We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COM... more We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Single increasing oral doses of entacapone (50-400 mg) were administered concomitantly with a single oral dose of levodopa/carbidopa (100/25 mg). The subjects were treated with carbidopa (100 mg t.i.d.) for 1 day prior to the administration of study drugs. Plasma concentrations of levodopa; its metabolites 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA); as well as carbidopa and entacapone were determined for pharmacokinetic calculations. Entacapone dose-dependently increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was 65% after the 400 mg dose of entacapone. Neither Cmax nor Tmax of levodopa was statistically significantly influenced by entacapone. Entacapone dose-dependently decreased the AUC of 3-OMD, maximally by 58%. The AUC of DOPAC was statistically significantly increased but no change in the AUC of HVA was observed after entacapone. No drug-related adverse events or hemodynamic effects were observed. The in vivo biochemical effects of entacapone indicate that it is an orally active COMT inhibitor and that it may improve the therapeutic efficacy of levodopa in Parkinson's disease.
To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson&... more To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson's disease (PD) severity in a common patient management setting in Finland.Scope. Two hundred and sixty consecutive outpatients with idiopathic PD participated. UPDRS, motor fluctuations, QoL, and the use of health care resources were measured. Direct and indirect costs were calculated. There is a strong relationship between QoL or cost-of-illness on the one hand, and severity of PD on the other. Treatment policies capable of reducing or delaying motor fluctuations would be expected to increase QoL and reduce some of the economic burden of PD.
Twenty-five epileptic outpatients were studied to assess possible effects of the first 6 months o... more Twenty-five epileptic outpatients were studied to assess possible effects of the first 6 months of treatment with carbamazepine or oxcarbazepine using serial peripheral nerve conduction measurements. Carbamazepine caused a small slowing effect on the motor conduction of the median nerve after 4 weeks of treatment, and the effect was correlated with the fasting serum concentration of the drug. Slowed motor conduction value of the median nerve was also observed after 6 months of treatment with carbamazepine. Oxcarbazepine did not cause any statistically significant slowing of nerve conduction.
Summary: The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine ... more Summary: The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine derivative, were studied in this open clinical trial in 27 patients with severe epilepsy resistant to conventional drugs. After the 2–week control phase, taltrimide was given in gradually increasing doses up to 4.0 g/ day—this dose used for 12 days. Taltrimide was given over 4 weeks and it was gradually withdrawn over 2 weeks. The frequency of seizures increased statistically significantly during the trial with increasing dose of taltrimide and decreased again in the withdrawal phase of the trial. Of six dropouts, one had status epilepticus, and in two patients increased number or severity of seizures necessitated withdrawal of taltrimide. There were no changes in EEG recordings or in laboratory data for safety evaluation. Taltrimide penetrated well through the blood‐brain barrier, with the concentration of its main metabolite, phthalimidoethanesulphonamide, in cerebrospinal fluid, about half that in serum. The concentration of phenytoin increased statistically significantly, and there was a significant decrease in serum carbamazepine concentration during the taltrimide treatment. The anticonvulsive effect of taltrimide observed in animal experiments could not be confirmed in this study; in contrast, the seizures increased statistically significantly during taltrimide treatment. The reason for this remains obscure. The doses used, the significant drug interactions, or the patient material seemingly do not explain totally the noticed increase in seizure frequency. One explanation may be that taltrimide has preconvulsive properties in humans.RESUMELa Taurine est un des amino‐acides considérés comme ayant des effets antiepileptiques. La concentration de taurine est modifiée dans le cerveau épileptique et son administration, systémique ou locale, supprime l'épilepsie dans de nombreux modèles animaux et dans quelques travaux cliniques (van Gleder, 1972; Bergamini et al., 1974; Airaksinen et al., 1980). Les résultats sont cependant controversés. Une des explications en est la faible pénétration de la taurine à travers la barrière hémato‐encéphalique (Barbeau et al., 1975; van Gelder, 1978). La Taltrimide (phthalimidoethanesulphon‐N‐isopropylamide) est un dérivé lipophile de la Taurine qui pénètre bien dans le cerveau (Lindén et al., 1982). La Taltrimide orale a un effet anticonvulsivant évident dans les modèles expérimentaux d'épilepsie aiguë (e.g., crise maximale à l'électrochoc, seuil critique au pentylentetrazol) l'ED50 étant de l'ordre de 100 à 300 mg/kg chez la souris (Lindén et al., 1982; Oja et al., 1983). Ce travial présente les résultats d'une étude clinique ouverte de la Taltrimide. Nous avons étudié son action anti‐épileptique, ses effets sur l'électroencéphologramme (EEG) et sa tolérance chez des patients ayant une épilepsie sévère résistant aux drogues conventionnelles.RESUMENLa taurina es un aminoácido al que se le achaean efectos antiepilépticos. La concentración de taurina está alterada en el cerebro epiléptico y la administración local o sistémica de esta droga ha mostrado tener efectos supresores sobre la epilepsia en muchos modelos animales y también en algunos estudios clínicos (van Gleder, 1972; Bergamini et al., 1974; Airaksinen et al., 1980). De todos modos los resultados han ofrecido bastante controversia. Una explicación para esto puede encontrarse en la escasa penetración de la taurina a través de la barrera hematoencefálica (Barbeau et al., 1975; van Gelder, 1978). La taltrimida (ftalimidoetanosulfona‐N‐isopropilamida) es un derivado lipofílico de la taurina que penetra bien en el cerebro (Lindén et al., 1982). La taltrimida oral tiene efectos anticonvulsives claros en modelos de ataques experimentales agudos (p.ej. ataques al máximo electroshock, ataques secundarios al pentilentetrazol) siendo la ED50 del orden de los 100–300 mg/kg en el raton (Linden et al., 1982; Oja et al., 1983). En esta comunicación se presentan los resultados de un ensayo clínico abierto con la taltrimida en el que se ha estudiado su efecto antiepiléptico, así como los efectos sobre el EEG y su tolerancia en pacientes con epilepsia severa resistente a medicaciones convencionales.ZUSAMMENFASSUNGTaurin ist eine der Aminosäuren die angeblich antiepileptische Wirkungen entfaltet. Es wurde nachgewiesen, daß die Konzentration des Taurin im epileptisch veränderten Gehirn und seine lokale oder systemische Anwendung in der Lage ist, in vielen Tiermodellen und auch in einigen klinischen Studien die Epilepsie zu unterdriicken (van Gleder, 1972; Bergamini et al, 1974; Airaksinen et al, 1980). Die Ergebnisse sind jedoch widersprüchlich. Eine Erklärung dafür könnte in der schlechten Penetration des Taurins durch die Bluthirnschranke liegen (Barbeau et al, 1975; van Gelder, 1978). Taltrimid (Phthalimidoethansulphon‐N‐Isopropylamid) ist ein lipophiles Taurin‐Derivat, das gut ins Hirn penetriert (Lindén et al, 1982). Die orale…
Oxcarbazepine (10.11-dihydro-10-oxo-carbamazepine, GP 47.680, O X C ) i s a new a n t i e p i l e... more Oxcarbazepine (10.11-dihydro-10-oxo-carbamazepine, GP 47.680, O X C ) i s a new a n t i e p i l e p t i c drug c lose ly r e l a t ed t o carbamazepine ( C B Z ) . In man O X C i s rap id ly and almost completely converted t o 10-OH-carbazepine ( 1 , 2 ) . In animal s tud ies both OXC and 10-OH-carbazepine have had s i m i l a r a n t i e p i l e p t i c e f f e c t s t o tha t of CBZ ( 3 ) . T h i s has been confirmed i n preliminary c l i n i c a l s tud ie s (4 ) . In c l i n i c a l s tud ie s O X C has been b e t t e r t o l e ra t ed t h a n CBZ.
When erythromycin (ERY) is co-administrated with the antiepileptic carbamazepine (CBZ), a drug in... more When erythromycin (ERY) is co-administrated with the antiepileptic carbamazepine (CBZ), a drug interaction may cause an increase in CBZ plasma concentrations, which can result in CBZ related toxic symptoms. This cross-over study was designated to investigate whether ERY influences the pharmacokinetics of the new antiepileptic oxcarbazepine (OXC) and its metabolites. In 8 healthy volunteers there were no significant differences in AUC, peak plasma concentrations or time to peak concentration when OXC was administered either with or without ERY. The results of this study suggest that OXC may offer an important advantage over CBZ especially when concomitant therapy with ERY is required.
Taurine shows anticonvulsive action i n many animal models o f epilepsy (e.9. van Gelder, N. M., ... more Taurine shows anticonvulsive action i n many animal models o f epilepsy (e.9. van Gelder, N. M., (1972) Brain Res. 47, 157-165). There are, however, confl ict ing reports on i t s anticonvulsive effects in cl inical studies af ter systemic administration, possibly due to a poor penetration through blood-brain barrier (Bergamini, L., R. Mutani, M. Delsedine & L. Durel l i , (1974) Europ. Neurol. 11, 261-269; Airaksinen, E. M., S. S. Oja, K.-M. Marnela, E. Leino & L. Paakkonen, (1980) in Clinical and Biological Research Vol. 39:157-166, ed: L. Battistin, G. Hashin, A. Lajtha. Alan R. Liss, New York; Takahashi, R. & Yoshibumi Nakane, (1978) i n Taurine and Neurological Disorders, 375-385, ed: A. Barbeau & R. J. Huxtable. Raven Press, New York). taurine and i ts derivatives are not wel l clari f ied a t present.
The effects of single and repeated doses of oral activated charcoal (OAC) on the absorption and e... more The effects of single and repeated doses of oral activated charcoal (OAC) on the absorption and elimination of the antiepileptic drugs, lamotrigine (CAS 84057-84-1, LTG, Lamictal) and oxcarbazepine (CAS 28721-07-5, OXC, Trileptal) were studied in healthy volunteers to assess the therapeutic potential of OAC in the treatment of LTG and OXC overdose. In three open, randomized, cross-over sessions with > or = 14 days washout, LTG 100 mg and OXC 600 mg were given orally, each to 6 subjects. In one session the drugs were given alone, and in two others with single (50 g) or repeated (20 g) doses of OAC as water suspension. The single OAC dose was given 30 min after the drugs, and repeated doses 6-72 h after LTG and 12-48 h after OXC. Serum concentrations of the parent drugs as well as those of the pharmacolocigally active metabolite of OXC, 10,11-dihydro-10-hydroxy-carbamazepine (MHD), were measured with reverse-phase high-performance liquid chromatography. Pharmacokinetic variables were calculated by non-compartmental analysis. Single OAC dose decreased AUC0-infinity of LTG, OXC and MHD to 58%, 2.8% and 4.2% of the respective variables without OAC. Also Tmax of OXC and MHD decreased to 4.4% and 8.1%, respectively. Repeated OAC doses after LTG decreased its AUC from 6 h to infinity (AUC6-infinity) to 39% and t1/21beta to 44%. Repeated OAC doses after a single dose of OXC decreased the AUC12-infinity and t/12beta of MHD to 46% and 45% of the respective variables without OAC. OAC greatly reduces gastrointestinal absorption of LTG and especially that of OXC, and it accelerates the elimination of LTG and MHD. The use of OAC is hence strongly favoured in the treatment of overdose with these drugs.
In the quantification of symptoms of Parkinson's disease (PD), healthcare professional assessment... more In the quantification of symptoms of Parkinson's disease (PD), healthcare professional assessments, patient reported outcomes (PRO), and medical device grade wearables are currently used. Recently, also commercially available smartphones and wearable devices have been actively researched in the detection of PD symptoms. The continuous, longitudinal, and automated detection of motor and especially non-motor symptoms with these devices is still a challenge that requires more research. The data collected from everyday life can be noisy and frequently contains artefacts, and novel detection methods and algorithms are therefore needed. 42 PD patients and 23 control subjects were monitored with Garmin Vivosmart 4 wearable device and asked to fill a symptom and medication diary with a mobile application, at home, for about four weeks. Subsequent analyses are based on continuous accelerometer data from the device. Accelerometer data from the Levodopa Response Study (MJFFd) were reanalyzed, with symptoms quantified with linear spectral models trained on expert evaluations present in the data. Variational autoencoders (VAE) were trained on both our study accelerometer data and on MJFFd to detect movement states (e.g., walking, standing). A total of 7590 self-reported symptoms were recorded during the study. 88.9% (32/36) of PD patients, 80.0% (4/5) of DBS PD patients and 95.5% (21/ 22) of control subjects reported that using the wearable device was very easy or easy. Recording a symptom at the time of the event was assessed as very easy or easy by 70.1% (29/41) of subjects with PD. Aggregated spectrograms of the collected accelerometer data show relative attenuation of low (<5Hz) frequencies in patients. Similar spectral patterns also separate symptom periods from immediately adjacent non-symptomatic periods. Discriminative power of linear models to separate symptoms from adjacent periods is weak, but aggregates show partial separability of patients vs. controls. The analysis reveals differential PLOS DIGITAL HEALTH
Parkinson's disease (PD) is a common neurodegenerative disorder that affects mainly the elderly p... more Parkinson's disease (PD) is a common neurodegenerative disorder that affects mainly the elderly population causing a progressive functional disability with motor, psychic, and cognitive deterioration. PD carries an increased risk of nursing home placement [1-3]. In fact, together with stroke and dementia, PD is one of the leading causes of institutionalization [2,4]. The reported prevalence of PD patients among nursing home residents is in the range from 1.6 to 7% [2,5-9]. Prospective cohort studies have indicated that 20-53% of PD patients will eventually require housing in long-term care facilities [3,10,11]. Two previous studies reported that the point prevalence of PD patients who are institutionalized was 14% [3,9]. The risk factors for institutionalization in PD patients have been evaluated in a number of studies [6,10,12].
European Journal of Clinical Pharmacology, Dec 1, 1993
In an open, randomised, cross-over study we investigated the effect of a single 200 mg oral dose ... more In an open, randomised, cross-over study we investigated the effect of a single 200 mg oral dose of entacapone, a novel catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa/carbidopa, and on the cardiovascular responses (blood pressure and pulse rate variation to standard stimuli) in eight parkinsonian patients. Entacapone significantly increased the mean area under the plasma concentration curve (AUC) of levodopa by 46%, from 3620 to 5280 h.ng.ml-1 and prolonged its elimination half-life (t1/2el) from 1.5 h to 2.0 h. The mean AUC of 3,4-dihydroxyphenylacetic acid (DOPAC), the monoamine oxidase-dependent metabolite of levodopa, was significantly increased from 122 to 343 h.micrograms.ml-1 by entacapone. A small decrease in the AUC of homovanillic acid (HVA), the COMT dependent metabolite of levodopa, was observed (from 455 to 303 h.ng.ml-1). Entacapone also decreased the excretion of HVA but not that of 3-methoxytyramine in the urine. Cardiovascular autonomic responses to sympathetic and parasympathetic stimuli were not changed by entacapone. We conclude that a single dose of entacapone moderately increases the AUC and prolongs the t1/2el of levodopa in man and that that does not affect cardiovascular autonomic regulation.
We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COM... more We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Single increasing oral doses of entacapone (50-400 mg) were administered concomitantly with a single oral dose of levodopa/carbidopa (100/25 mg). The subjects were treated with carbidopa (100 mg t.i.d.) for 1 day prior to the administration of study drugs. Plasma concentrations of levodopa; its metabolites 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA); as well as carbidopa and entacapone were determined for pharmacokinetic calculations. Entacapone dose-dependently increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was 65% after the 400 mg dose of entacapone. Neither Cmax nor Tmax of levodopa was statistically significantly influenced by entacapone. Entacapone dose-dependently decreased the AUC of 3-OMD, maximally by 58%. The AUC of DOPAC was statistically significantly increased but no change in the AUC of HVA was observed after entacapone. No drug-related adverse events or hemodynamic effects were observed. The in vivo biochemical effects of entacapone indicate that it is an orally active COMT inhibitor and that it may improve the therapeutic efficacy of levodopa in Parkinson&amp;amp;#39;s disease.
To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson&... more To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson&#39;s disease (PD) severity in a common patient management setting in Finland.Scope. Two hundred and sixty consecutive outpatients with idiopathic PD participated. UPDRS, motor fluctuations, QoL, and the use of health care resources were measured. Direct and indirect costs were calculated. There is a strong relationship between QoL or cost-of-illness on the one hand, and severity of PD on the other. Treatment policies capable of reducing or delaying motor fluctuations would be expected to increase QoL and reduce some of the economic burden of PD.
Twenty-five epileptic outpatients were studied to assess possible effects of the first 6 months o... more Twenty-five epileptic outpatients were studied to assess possible effects of the first 6 months of treatment with carbamazepine or oxcarbazepine using serial peripheral nerve conduction measurements. Carbamazepine caused a small slowing effect on the motor conduction of the median nerve after 4 weeks of treatment, and the effect was correlated with the fasting serum concentration of the drug. Slowed motor conduction value of the median nerve was also observed after 6 months of treatment with carbamazepine. Oxcarbazepine did not cause any statistically significant slowing of nerve conduction.
Summary: The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine ... more Summary: The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine derivative, were studied in this open clinical trial in 27 patients with severe epilepsy resistant to conventional drugs. After the 2–week control phase, taltrimide was given in gradually increasing doses up to 4.0 g/ day—this dose used for 12 days. Taltrimide was given over 4 weeks and it was gradually withdrawn over 2 weeks. The frequency of seizures increased statistically significantly during the trial with increasing dose of taltrimide and decreased again in the withdrawal phase of the trial. Of six dropouts, one had status epilepticus, and in two patients increased number or severity of seizures necessitated withdrawal of taltrimide. There were no changes in EEG recordings or in laboratory data for safety evaluation. Taltrimide penetrated well through the blood‐brain barrier, with the concentration of its main metabolite, phthalimidoethanesulphonamide, in cerebrospinal fluid, about half that in serum. The concentration of phenytoin increased statistically significantly, and there was a significant decrease in serum carbamazepine concentration during the taltrimide treatment. The anticonvulsive effect of taltrimide observed in animal experiments could not be confirmed in this study; in contrast, the seizures increased statistically significantly during taltrimide treatment. The reason for this remains obscure. The doses used, the significant drug interactions, or the patient material seemingly do not explain totally the noticed increase in seizure frequency. One explanation may be that taltrimide has preconvulsive properties in humans.RESUMELa Taurine est un des amino‐acides considérés comme ayant des effets antiepileptiques. La concentration de taurine est modifiée dans le cerveau épileptique et son administration, systémique ou locale, supprime l'épilepsie dans de nombreux modèles animaux et dans quelques travaux cliniques (van Gleder, 1972; Bergamini et al., 1974; Airaksinen et al., 1980). Les résultats sont cependant controversés. Une des explications en est la faible pénétration de la taurine à travers la barrière hémato‐encéphalique (Barbeau et al., 1975; van Gelder, 1978). La Taltrimide (phthalimidoethanesulphon‐N‐isopropylamide) est un dérivé lipophile de la Taurine qui pénètre bien dans le cerveau (Lindén et al., 1982). La Taltrimide orale a un effet anticonvulsivant évident dans les modèles expérimentaux d'épilepsie aiguë (e.g., crise maximale à l'électrochoc, seuil critique au pentylentetrazol) l'ED50 étant de l'ordre de 100 à 300 mg/kg chez la souris (Lindén et al., 1982; Oja et al., 1983). Ce travial présente les résultats d'une étude clinique ouverte de la Taltrimide. Nous avons étudié son action anti‐épileptique, ses effets sur l'électroencéphologramme (EEG) et sa tolérance chez des patients ayant une épilepsie sévère résistant aux drogues conventionnelles.RESUMENLa taurina es un aminoácido al que se le achaean efectos antiepilépticos. La concentración de taurina está alterada en el cerebro epiléptico y la administración local o sistémica de esta droga ha mostrado tener efectos supresores sobre la epilepsia en muchos modelos animales y también en algunos estudios clínicos (van Gleder, 1972; Bergamini et al., 1974; Airaksinen et al., 1980). De todos modos los resultados han ofrecido bastante controversia. Una explicación para esto puede encontrarse en la escasa penetración de la taurina a través de la barrera hematoencefálica (Barbeau et al., 1975; van Gelder, 1978). La taltrimida (ftalimidoetanosulfona‐N‐isopropilamida) es un derivado lipofílico de la taurina que penetra bien en el cerebro (Lindén et al., 1982). La taltrimida oral tiene efectos anticonvulsives claros en modelos de ataques experimentales agudos (p.ej. ataques al máximo electroshock, ataques secundarios al pentilentetrazol) siendo la ED50 del orden de los 100–300 mg/kg en el raton (Linden et al., 1982; Oja et al., 1983). En esta comunicación se presentan los resultados de un ensayo clínico abierto con la taltrimida en el que se ha estudiado su efecto antiepiléptico, así como los efectos sobre el EEG y su tolerancia en pacientes con epilepsia severa resistente a medicaciones convencionales.ZUSAMMENFASSUNGTaurin ist eine der Aminosäuren die angeblich antiepileptische Wirkungen entfaltet. Es wurde nachgewiesen, daß die Konzentration des Taurin im epileptisch veränderten Gehirn und seine lokale oder systemische Anwendung in der Lage ist, in vielen Tiermodellen und auch in einigen klinischen Studien die Epilepsie zu unterdriicken (van Gleder, 1972; Bergamini et al, 1974; Airaksinen et al, 1980). Die Ergebnisse sind jedoch widersprüchlich. Eine Erklärung dafür könnte in der schlechten Penetration des Taurins durch die Bluthirnschranke liegen (Barbeau et al, 1975; van Gelder, 1978). Taltrimid (Phthalimidoethansulphon‐N‐Isopropylamid) ist ein lipophiles Taurin‐Derivat, das gut ins Hirn penetriert (Lindén et al, 1982). Die orale…
Oxcarbazepine (10.11-dihydro-10-oxo-carbamazepine, GP 47.680, O X C ) i s a new a n t i e p i l e... more Oxcarbazepine (10.11-dihydro-10-oxo-carbamazepine, GP 47.680, O X C ) i s a new a n t i e p i l e p t i c drug c lose ly r e l a t ed t o carbamazepine ( C B Z ) . In man O X C i s rap id ly and almost completely converted t o 10-OH-carbazepine ( 1 , 2 ) . In animal s tud ies both OXC and 10-OH-carbazepine have had s i m i l a r a n t i e p i l e p t i c e f f e c t s t o tha t of CBZ ( 3 ) . T h i s has been confirmed i n preliminary c l i n i c a l s tud ie s (4 ) . In c l i n i c a l s tud ie s O X C has been b e t t e r t o l e ra t ed t h a n CBZ.
When erythromycin (ERY) is co-administrated with the antiepileptic carbamazepine (CBZ), a drug in... more When erythromycin (ERY) is co-administrated with the antiepileptic carbamazepine (CBZ), a drug interaction may cause an increase in CBZ plasma concentrations, which can result in CBZ related toxic symptoms. This cross-over study was designated to investigate whether ERY influences the pharmacokinetics of the new antiepileptic oxcarbazepine (OXC) and its metabolites. In 8 healthy volunteers there were no significant differences in AUC, peak plasma concentrations or time to peak concentration when OXC was administered either with or without ERY. The results of this study suggest that OXC may offer an important advantage over CBZ especially when concomitant therapy with ERY is required.
Taurine shows anticonvulsive action i n many animal models o f epilepsy (e.9. van Gelder, N. M., ... more Taurine shows anticonvulsive action i n many animal models o f epilepsy (e.9. van Gelder, N. M., (1972) Brain Res. 47, 157-165). There are, however, confl ict ing reports on i t s anticonvulsive effects in cl inical studies af ter systemic administration, possibly due to a poor penetration through blood-brain barrier (Bergamini, L., R. Mutani, M. Delsedine & L. Durel l i , (1974) Europ. Neurol. 11, 261-269; Airaksinen, E. M., S. S. Oja, K.-M. Marnela, E. Leino & L. Paakkonen, (1980) in Clinical and Biological Research Vol. 39:157-166, ed: L. Battistin, G. Hashin, A. Lajtha. Alan R. Liss, New York; Takahashi, R. & Yoshibumi Nakane, (1978) i n Taurine and Neurological Disorders, 375-385, ed: A. Barbeau & R. J. Huxtable. Raven Press, New York). taurine and i ts derivatives are not wel l clari f ied a t present.
The effects of single and repeated doses of oral activated charcoal (OAC) on the absorption and e... more The effects of single and repeated doses of oral activated charcoal (OAC) on the absorption and elimination of the antiepileptic drugs, lamotrigine (CAS 84057-84-1, LTG, Lamictal) and oxcarbazepine (CAS 28721-07-5, OXC, Trileptal) were studied in healthy volunteers to assess the therapeutic potential of OAC in the treatment of LTG and OXC overdose. In three open, randomized, cross-over sessions with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 14 days washout, LTG 100 mg and OXC 600 mg were given orally, each to 6 subjects. In one session the drugs were given alone, and in two others with single (50 g) or repeated (20 g) doses of OAC as water suspension. The single OAC dose was given 30 min after the drugs, and repeated doses 6-72 h after LTG and 12-48 h after OXC. Serum concentrations of the parent drugs as well as those of the pharmacolocigally active metabolite of OXC, 10,11-dihydro-10-hydroxy-carbamazepine (MHD), were measured with reverse-phase high-performance liquid chromatography. Pharmacokinetic variables were calculated by non-compartmental analysis. Single OAC dose decreased AUC0-infinity of LTG, OXC and MHD to 58%, 2.8% and 4.2% of the respective variables without OAC. Also Tmax of OXC and MHD decreased to 4.4% and 8.1%, respectively. Repeated OAC doses after LTG decreased its AUC from 6 h to infinity (AUC6-infinity) to 39% and t1/21beta to 44%. Repeated OAC doses after a single dose of OXC decreased the AUC12-infinity and t/12beta of MHD to 46% and 45% of the respective variables without OAC. OAC greatly reduces gastrointestinal absorption of LTG and especially that of OXC, and it accelerates the elimination of LTG and MHD. The use of OAC is hence strongly favoured in the treatment of overdose with these drugs.
In the quantification of symptoms of Parkinson's disease (PD), healthcare professional assessment... more In the quantification of symptoms of Parkinson's disease (PD), healthcare professional assessments, patient reported outcomes (PRO), and medical device grade wearables are currently used. Recently, also commercially available smartphones and wearable devices have been actively researched in the detection of PD symptoms. The continuous, longitudinal, and automated detection of motor and especially non-motor symptoms with these devices is still a challenge that requires more research. The data collected from everyday life can be noisy and frequently contains artefacts, and novel detection methods and algorithms are therefore needed. 42 PD patients and 23 control subjects were monitored with Garmin Vivosmart 4 wearable device and asked to fill a symptom and medication diary with a mobile application, at home, for about four weeks. Subsequent analyses are based on continuous accelerometer data from the device. Accelerometer data from the Levodopa Response Study (MJFFd) were reanalyzed, with symptoms quantified with linear spectral models trained on expert evaluations present in the data. Variational autoencoders (VAE) were trained on both our study accelerometer data and on MJFFd to detect movement states (e.g., walking, standing). A total of 7590 self-reported symptoms were recorded during the study. 88.9% (32/36) of PD patients, 80.0% (4/5) of DBS PD patients and 95.5% (21/ 22) of control subjects reported that using the wearable device was very easy or easy. Recording a symptom at the time of the event was assessed as very easy or easy by 70.1% (29/41) of subjects with PD. Aggregated spectrograms of the collected accelerometer data show relative attenuation of low (<5Hz) frequencies in patients. Similar spectral patterns also separate symptom periods from immediately adjacent non-symptomatic periods. Discriminative power of linear models to separate symptoms from adjacent periods is weak, but aggregates show partial separability of patients vs. controls. The analysis reveals differential PLOS DIGITAL HEALTH
Parkinson's disease (PD) is a common neurodegenerative disorder that affects mainly the elderly p... more Parkinson's disease (PD) is a common neurodegenerative disorder that affects mainly the elderly population causing a progressive functional disability with motor, psychic, and cognitive deterioration. PD carries an increased risk of nursing home placement [1-3]. In fact, together with stroke and dementia, PD is one of the leading causes of institutionalization [2,4]. The reported prevalence of PD patients among nursing home residents is in the range from 1.6 to 7% [2,5-9]. Prospective cohort studies have indicated that 20-53% of PD patients will eventually require housing in long-term care facilities [3,10,11]. Two previous studies reported that the point prevalence of PD patients who are institutionalized was 14% [3,9]. The risk factors for institutionalization in PD patients have been evaluated in a number of studies [6,10,12].
European Journal of Clinical Pharmacology, Dec 1, 1993
In an open, randomised, cross-over study we investigated the effect of a single 200 mg oral dose ... more In an open, randomised, cross-over study we investigated the effect of a single 200 mg oral dose of entacapone, a novel catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa/carbidopa, and on the cardiovascular responses (blood pressure and pulse rate variation to standard stimuli) in eight parkinsonian patients. Entacapone significantly increased the mean area under the plasma concentration curve (AUC) of levodopa by 46%, from 3620 to 5280 h.ng.ml-1 and prolonged its elimination half-life (t1/2el) from 1.5 h to 2.0 h. The mean AUC of 3,4-dihydroxyphenylacetic acid (DOPAC), the monoamine oxidase-dependent metabolite of levodopa, was significantly increased from 122 to 343 h.micrograms.ml-1 by entacapone. A small decrease in the AUC of homovanillic acid (HVA), the COMT dependent metabolite of levodopa, was observed (from 455 to 303 h.ng.ml-1). Entacapone also decreased the excretion of HVA but not that of 3-methoxytyramine in the urine. Cardiovascular autonomic responses to sympathetic and parasympathetic stimuli were not changed by entacapone. We conclude that a single dose of entacapone moderately increases the AUC and prolongs the t1/2el of levodopa in man and that that does not affect cardiovascular autonomic regulation.
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