ing ordered the way they appear in the document. The editors and authors appear to be well publis... more ing ordered the way they appear in the document. The editors and authors appear to be well published in the field. However, in the “List of Contributors” section, it is hard to distinguish where they practice. That is, some authors are listed from Goteburg, Lund, and Sjobo, and an English-speaking reader may not know where these places are. The contributors’ positions and places of employment should appear in the same format to avoid confusion. I am not familiar with other textbooks in this field; therefore, I cannot draw a comparison. I am familiar with sections of textbooks regarding obesity and, certainly, as intended, this book is a much more extensive review of prevention and treatment of obesity. Although I am not familiar with the pricing of books, I believe $140 to be excessive. Granted, a lot of work went into the publication of this book; however, texts that are much more extensive in content sometimes cost around the same price or a little more. I think the range of $50–70 is much more reasonable. The intended audience is healthcare professionals; this is not written for lay persons. I do not recommend this book for purchase by an individual or library. However, if future editions undergo significant editing and revision, I could see it being a valuable purchase for dieticians, physicians, or other healthcare practitioners highly involved in nutrition counseling or management, as well as for medical libraries serving such professionals.
suppression modulated by environmental agents. This section discusses both environmental toxins a... more suppression modulated by environmental agents. This section discusses both environmental toxins and therapeutic agents. The chapters are well organized; however, the second section would have been clearer if it had been divided into sections on immunosuppression by environmental toxins, immunosuppression by therapeutic agents, and immunosuppression by drugs of abuse. The next four sections provide a comprehensive discussion of immunotoxicity in the lung, skin, general autoimmunity, and selective organs prone to immune damage such as the liver. The last two sections of the book provide an extensive review of hypersensitivity induced by chemical agents. It is confusing that therapeutic agents are included with environmental toxins in the discussion of hypersensitivity. As an immunotoxicologist, I believe the chapters in this book are well referenced, including classic key references in immunotoxicology. This text is for research scientists interested in exploring the role of the immune system and toxic agents. Although the chapters do not go into specific research methods that can be transferred into the scientist's laboratory, the references are complete enough that the researcher can access the articles that contain the research methods. With the exception of the chapters on transplant agents and respiratory hypersensitivity to chemicals, the text would have been better understood with more graphs and diagrams. This book is a valuable resource for toxicologists interested in immune-mediated toxicity. Although the first part of the book presents a review of the immune system in animal models, the reader should have a basic knowledge of immunology to read this text. It is complete and reasonably priced for the intended audience. I recommend this book for scientists interested in immunotoxicology.
In one experiment, 5 dogs were administered digoxin (0.022 mg/kg of body weight, IV), were rested... more In one experiment, 5 dogs were administered digoxin (0.022 mg/kg of body weight, IV), were rested for 2 weeks, were then given phenobarbital (13.2 mg/kg orally) for 14 days, and then were given digoxin again (0.022 mg/kg, IV). Comparing prephenobarbital (control) digoxin half-lives of 42.4 +/- 8.8 hours and postphenobarbital digoxin half-lives of 18.0 +/- 2.2 hours, the half-life was significantly (P less than 0.05) decreased after phenobarbital administration. Clearance was increased by 84%, and the volume of distribution given was decreased by 34%. In a second experiment, 5 dogs were given digoxin (0.022 mg/kg, orally) daily for 11 days, and the digoxin kinetics were evaluated after the last dosing. The dogs were then rested and given phenobarbital (13.2 mg/kg, orally) once daily for 14 days and digoxin (0.022 mg/kg) once daily for 11 days, and the pharmacokinetics of digoxin was determined on the last day of dosing. Significant differences in steady-state serum concentrations and...
Pharmacokinetics of phenobarbital was studied in 10 healthy dogs after single IV or oral administ... more Pharmacokinetics of phenobarbital was studied in 10 healthy dogs after single IV or oral administration. Phenobarbital sodium was administered IV to 5 dogs in group A (5.5 mg/kg of body weight) and 5 dogs in group B (15 mg/kg). Serial venous blood samples (n = 21) were collected from each dog before (base line) and after the administration of phenobarbital sodium for pharmacokinetic evaluation. After a 30-day resting period, 3 dogs in group A and 3 in group B were randomly selected and used for an IV crossover treatment. The IV treatment mean half-life of phenobarbital sodium was 92.6 +/- 23.7 and 72.3 +/- 15.5 hours, whereas mean total clearance was 5.60 +/- 2.31 and 6.66 +/- 0.78 ml/hr/kg for doses of 5 and 15 mg/kg, respectively. The mean residence time was 124 +/- 34 hours and 106 +/- 23 hours for the 5.5 and 15 mg/kg, IV doses, respectively. Significant differences (P greater than 0.05) were not observed in pharmacokinetic parameters between the 2-dose study. After a 35-day res...
Sodium phenobarbital (PHB) was administered orally as tablets 3 times a day to 6 healthy mature d... more Sodium phenobarbital (PHB) was administered orally as tablets 3 times a day to 6 healthy mature dogs of mixed breeding for 5 days at a dose of 2 mg/kg of body weight. On the 6th day, PHB was administered at 9 AM and venous blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 23, 35, 47, 59, 71, 83, 95, 107, 119, and 131 hours. Additional PHB was not given on day 6. Drug serum concentrations were described by a 1-compartment model with first-order absorption and elimination with fitted correlation coefficients of 0.991 +/- 0.007 (mean +/- SD). The observed PHB half-lives were between 37.3 and 74.6 hours with a mean of 53.0 +/- 15 hours. The calculated volume of distribution (Vd/F) was 743.6 +/- 69.8 ml/kg, and the total body clearance (ClT/F) was 0.173 +/- 0.053 ml/min/ kg. The absorption half-life was 1.27 +/- 0.21 hours. Based on the observed biological half-life after 5 days of dosing, approximately 11 days (8 to 15.5 days) of multiple dosing would be required to achie...
International journal of clinical pharmacology and therapeutics, 1996
Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly adm... more Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine the effect of cholestyramine on the plasma concentrations of valproic acid (VPA) following concurrent and staggered (VPA 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. In each phase fasting subjects received 250 mg of VPA followed by serial blood sampling for VPA plasma concentrations over a 37-hour period. In the concurrent and staggered phase the subjects received 4 g of cholestyramine (CHOL) twice daily 24 hours prior to and following the VPA dose. During the concurrent phase the coadministration of CHOL resulted in a decrease (p < 0.05) in the area under the curve (AUC) for VPA compared to VPA alone (415.2 +/- 113.2 mg*hr/l vs 489.2 +/- 153.0 mg*hr/l, respectively). When the same dose of each drug was administered 3 ho...
Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were s... more Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were surgically thyroidectomized and used in a Latin-square design pharmacokinetic study of orally administered L-thyroxine. The dogs were treated with 44, 22, and 11 micrograms of L-thyroxine/kg as a single morning dose or in divided doses, morning and evening. Serum concentration of thyroxine (T4) was evaluated to determine a number of pharmacokinetic variables for comparison. Mean steady-state concentrations (Css) were determined from the area under the curve. Variables were analyzed for comparisons between dosages by use of ANOVA. Concentration at steady state was highest for dogs of the 44-micrograms/kg of body weight once-daily group and was lowest for dogs of the group given 11 micrograms/kg in 2 daily doses. Single daily administration resulted in higher Css, except at the 22-micrograms/kg/d dosage. Clearance was faster for the 22- and 44-micrograms/kg/d dosages than for the 11-microgr...
International journal of clinical pharmacology and therapeutics, 1994
Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly adm... more Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine cholestyramine effect on the plasma concentrations of sulindac and its sulfide metabolite following concurrent and staggered (sulindac 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. Subjects received 400 mg sulindac orally followed by serial blood sampling for sulindac and sulindac sulfide plasma concentrations over a 24-hour period. During the concurrent phase, 4 g of cholestyramine was coadministered resulting in a decrease (p < 0.05) in the area under the curve (AUC) for sulindac compared to sulindac alone (7.11 +/- 3.25 micrograms-h/ml vs 31.65 +/- 7.94 micrograms-h/ml respectively). Also, the sulindac sulfide AUC decreased (p < 0.05) to 7.26 +/- 4.37 micrograms-h/ml coadministration of both drugs compared to 44.69 ...
Tritium-labeled prednisolone sodium succinate was administered IV to 4 healthy, awake, nonsplenec... more Tritium-labeled prednisolone sodium succinate was administered IV to 4 healthy, awake, nonsplenectomized dogs. The concentration of prednisolone and its metabolites in the plasma were measured for 10 hours. Forty-one percent of the blood volume of these dogs was removed, and plasma prednisolone was measured again. The data before and after hemorrhage were fitted to a 2-compartment open model. From plasma profiles, a rapid distributional phase, followed by a slower phase, was observed in control and shock groups. Volume of the central compartment of prednisolone before and after hemorrhage was 165 ml/kg of body weight and 110 ml/kg, respectively; and the difference was significant (P less than 0.05). The rate of total body clearance of prednisolone before and after hemorrhage was 3.96 ml/min/kg and 2.53 ml/min/kg, respectively; the difference was significant. The mean plasma half-lives for prednisolone sodium succinate and its metabolites, before and after hemorrhage, were 166 and 19...
Predictions of free (unbound) serum phenytoin concentration by three methods were compared with r... more Predictions of free (unbound) serum phenytoin concentration by three methods were compared with results obtained by the Abbott TDx Free Phenytoin ultrafiltration and fluorescence-polarization immunoassay technique. Data were obtained for hospitalized adults who had been receiving phenytoin for at least five days and were free of renal or hepatic disease. Total phenytoin concentration was determined, and free phenytoin concentration was measured in ultrafiltrate at 25 degrees C. For each patient, measured concentrations of total phenytoin and albumin were used to predict free phenytoin concentrations by the Gugler method, the Sheiner-Tozer nomogram, and the Sheiner-Tozer equation. Mean measured percentages of free phenytoin were 17.79%, 12.13%, and 8.73%, respectively, for patients with albumin concentrations of less than 2 g/dL (n = 5), 2-3 g/dL (n = 18), and greater than 3 g/dL (n = 26). There was a strong correlation between actual and predicted free phenytoin concentrations for e...
Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of bo... more Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive days. Seventeen venous blood samples were collected from each horse after the single dose study and again after the last dose on day 42. Plasma phenobarbital concentration was determined by use of a fluorescence assay validated for horses. Additional blood samples (n = 11) were collected on days 8 and 25 to determine peak and trough concentrations, as well as total body clearance. Phenobarbital disposition followed a one-compartment model. Mean kinetic variables after single and repeated orally administered doses (42 days) were: elimination half-life = 24.2 +/- 4.7 and 11.2 +/- 2.3 hours, volume of distribution = 0.960 +/- 0.060 and 0.914 +/- 0.119 L/kg, and clearance = 28.2 +/- 5.1 and 57.3 +/- 9.6 ml/h/kg, respectively. Results indicated that significant (P less than 0.05) difference in half-life and oral clearance ex...
An improved liquid chromatographic procedure is described for the quantitative determination of s... more An improved liquid chromatographic procedure is described for the quantitative determination of sulindac, sulindac sulfone, and sulindac sulfide from serum. The procedure makes use of acetonitrile extraction of the compounds of interest from acidified serum samples. Under these conditions extraction efficiencies in the 85 percent range are obtained for each of the compounds. The liquid chromatographic separation of the compounds of interest and the internal standard (indomethacin) is accomplished in an isocratic elution procedure using a nitrile (CN) stationary phase. The HPLC separation procedure is completed in less than 10 minutes, giving excellent resolution and peak shape.
Clinical and Experimental Pharmacology and Physiology, 1981
1. Digoxin was associated into phosphotidylcholine liposomes at concentrations of 28-33 mol% in H... more 1. Digoxin was associated into phosphotidylcholine liposomes at concentrations of 28-33 mol% in Hank&#39;s Buffer, pH 7.4 at 28 degrees C. 2. Digoxin-liposomes (digoxin concentration 0.022 mg/kg per dog per day) administered intravenously in five adult male dogs attained therapeutic serum concentrations (0.7-3.0 ng/ml) beginning with day 1 of administration. 3. Digoxin serum concentrations obtained by intravenous digoxin-liposomes compared favorably with normal oral digoxin administration (0.022 mg/kg per dog per day) in all 5 dogs monitoring serum digoxin levels for 7 days showed no significant (P &lt; 0.05) differences in mean serum digoxin concentrations +/- s.e.m. on 6 of 7 days of treatments.
This study was undertaken to compare the susceptibility to inactivation of isepamicin with amikac... more This study was undertaken to compare the susceptibility to inactivation of isepamicin with amikacin and gentamicin when exposed to different beta-lactams, beta-lactamase inhibitors, and heparin. The aminoglycosides (5, 10, 20, and 50 micrograms/ml) were incubated in human serum with ampicillin, azlocillin, aztreonam, carbenicillin, ceftazidime, piperacillin, and ticarcillin (100 and 600 micrograms/ml) and with clavulanate, cilastatin, 1:1 imipenemcilastatin, oxacillin, and sulbactam (20 and 120 micrograms/ml) for 48 h at 37 degrees C. Aminoglycoside concentrations were measured by fluorescence polarization immunoassay (FPI) after 0, 8, and 48 h of incubation and by radial diffusion bioassay after 48 h of incubation. Each of the three aminoglycosides was also added to whole blood containing either heparin (100 U/ml) or 0.5% EDTA as a control and assayed after 6 h by FPI. The degree of inactivation of isepamicin by the beta-lactams was significantly less than that by amikacin (P less ...
ing ordered the way they appear in the document. The editors and authors appear to be well publis... more ing ordered the way they appear in the document. The editors and authors appear to be well published in the field. However, in the “List of Contributors” section, it is hard to distinguish where they practice. That is, some authors are listed from Goteburg, Lund, and Sjobo, and an English-speaking reader may not know where these places are. The contributors’ positions and places of employment should appear in the same format to avoid confusion. I am not familiar with other textbooks in this field; therefore, I cannot draw a comparison. I am familiar with sections of textbooks regarding obesity and, certainly, as intended, this book is a much more extensive review of prevention and treatment of obesity. Although I am not familiar with the pricing of books, I believe $140 to be excessive. Granted, a lot of work went into the publication of this book; however, texts that are much more extensive in content sometimes cost around the same price or a little more. I think the range of $50–70 is much more reasonable. The intended audience is healthcare professionals; this is not written for lay persons. I do not recommend this book for purchase by an individual or library. However, if future editions undergo significant editing and revision, I could see it being a valuable purchase for dieticians, physicians, or other healthcare practitioners highly involved in nutrition counseling or management, as well as for medical libraries serving such professionals.
suppression modulated by environmental agents. This section discusses both environmental toxins a... more suppression modulated by environmental agents. This section discusses both environmental toxins and therapeutic agents. The chapters are well organized; however, the second section would have been clearer if it had been divided into sections on immunosuppression by environmental toxins, immunosuppression by therapeutic agents, and immunosuppression by drugs of abuse. The next four sections provide a comprehensive discussion of immunotoxicity in the lung, skin, general autoimmunity, and selective organs prone to immune damage such as the liver. The last two sections of the book provide an extensive review of hypersensitivity induced by chemical agents. It is confusing that therapeutic agents are included with environmental toxins in the discussion of hypersensitivity. As an immunotoxicologist, I believe the chapters in this book are well referenced, including classic key references in immunotoxicology. This text is for research scientists interested in exploring the role of the immune system and toxic agents. Although the chapters do not go into specific research methods that can be transferred into the scientist's laboratory, the references are complete enough that the researcher can access the articles that contain the research methods. With the exception of the chapters on transplant agents and respiratory hypersensitivity to chemicals, the text would have been better understood with more graphs and diagrams. This book is a valuable resource for toxicologists interested in immune-mediated toxicity. Although the first part of the book presents a review of the immune system in animal models, the reader should have a basic knowledge of immunology to read this text. It is complete and reasonably priced for the intended audience. I recommend this book for scientists interested in immunotoxicology.
In one experiment, 5 dogs were administered digoxin (0.022 mg/kg of body weight, IV), were rested... more In one experiment, 5 dogs were administered digoxin (0.022 mg/kg of body weight, IV), were rested for 2 weeks, were then given phenobarbital (13.2 mg/kg orally) for 14 days, and then were given digoxin again (0.022 mg/kg, IV). Comparing prephenobarbital (control) digoxin half-lives of 42.4 +/- 8.8 hours and postphenobarbital digoxin half-lives of 18.0 +/- 2.2 hours, the half-life was significantly (P less than 0.05) decreased after phenobarbital administration. Clearance was increased by 84%, and the volume of distribution given was decreased by 34%. In a second experiment, 5 dogs were given digoxin (0.022 mg/kg, orally) daily for 11 days, and the digoxin kinetics were evaluated after the last dosing. The dogs were then rested and given phenobarbital (13.2 mg/kg, orally) once daily for 14 days and digoxin (0.022 mg/kg) once daily for 11 days, and the pharmacokinetics of digoxin was determined on the last day of dosing. Significant differences in steady-state serum concentrations and...
Pharmacokinetics of phenobarbital was studied in 10 healthy dogs after single IV or oral administ... more Pharmacokinetics of phenobarbital was studied in 10 healthy dogs after single IV or oral administration. Phenobarbital sodium was administered IV to 5 dogs in group A (5.5 mg/kg of body weight) and 5 dogs in group B (15 mg/kg). Serial venous blood samples (n = 21) were collected from each dog before (base line) and after the administration of phenobarbital sodium for pharmacokinetic evaluation. After a 30-day resting period, 3 dogs in group A and 3 in group B were randomly selected and used for an IV crossover treatment. The IV treatment mean half-life of phenobarbital sodium was 92.6 +/- 23.7 and 72.3 +/- 15.5 hours, whereas mean total clearance was 5.60 +/- 2.31 and 6.66 +/- 0.78 ml/hr/kg for doses of 5 and 15 mg/kg, respectively. The mean residence time was 124 +/- 34 hours and 106 +/- 23 hours for the 5.5 and 15 mg/kg, IV doses, respectively. Significant differences (P greater than 0.05) were not observed in pharmacokinetic parameters between the 2-dose study. After a 35-day res...
Sodium phenobarbital (PHB) was administered orally as tablets 3 times a day to 6 healthy mature d... more Sodium phenobarbital (PHB) was administered orally as tablets 3 times a day to 6 healthy mature dogs of mixed breeding for 5 days at a dose of 2 mg/kg of body weight. On the 6th day, PHB was administered at 9 AM and venous blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 23, 35, 47, 59, 71, 83, 95, 107, 119, and 131 hours. Additional PHB was not given on day 6. Drug serum concentrations were described by a 1-compartment model with first-order absorption and elimination with fitted correlation coefficients of 0.991 +/- 0.007 (mean +/- SD). The observed PHB half-lives were between 37.3 and 74.6 hours with a mean of 53.0 +/- 15 hours. The calculated volume of distribution (Vd/F) was 743.6 +/- 69.8 ml/kg, and the total body clearance (ClT/F) was 0.173 +/- 0.053 ml/min/ kg. The absorption half-life was 1.27 +/- 0.21 hours. Based on the observed biological half-life after 5 days of dosing, approximately 11 days (8 to 15.5 days) of multiple dosing would be required to achie...
International journal of clinical pharmacology and therapeutics, 1996
Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly adm... more Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine the effect of cholestyramine on the plasma concentrations of valproic acid (VPA) following concurrent and staggered (VPA 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. In each phase fasting subjects received 250 mg of VPA followed by serial blood sampling for VPA plasma concentrations over a 37-hour period. In the concurrent and staggered phase the subjects received 4 g of cholestyramine (CHOL) twice daily 24 hours prior to and following the VPA dose. During the concurrent phase the coadministration of CHOL resulted in a decrease (p < 0.05) in the area under the curve (AUC) for VPA compared to VPA alone (415.2 +/- 113.2 mg*hr/l vs 489.2 +/- 153.0 mg*hr/l, respectively). When the same dose of each drug was administered 3 ho...
Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were s... more Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were surgically thyroidectomized and used in a Latin-square design pharmacokinetic study of orally administered L-thyroxine. The dogs were treated with 44, 22, and 11 micrograms of L-thyroxine/kg as a single morning dose or in divided doses, morning and evening. Serum concentration of thyroxine (T4) was evaluated to determine a number of pharmacokinetic variables for comparison. Mean steady-state concentrations (Css) were determined from the area under the curve. Variables were analyzed for comparisons between dosages by use of ANOVA. Concentration at steady state was highest for dogs of the 44-micrograms/kg of body weight once-daily group and was lowest for dogs of the group given 11 micrograms/kg in 2 daily doses. Single daily administration resulted in higher Css, except at the 22-micrograms/kg/d dosage. Clearance was faster for the 22- and 44-micrograms/kg/d dosages than for the 11-microgr...
International journal of clinical pharmacology and therapeutics, 1994
Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly adm... more Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine cholestyramine effect on the plasma concentrations of sulindac and its sulfide metabolite following concurrent and staggered (sulindac 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. Subjects received 400 mg sulindac orally followed by serial blood sampling for sulindac and sulindac sulfide plasma concentrations over a 24-hour period. During the concurrent phase, 4 g of cholestyramine was coadministered resulting in a decrease (p < 0.05) in the area under the curve (AUC) for sulindac compared to sulindac alone (7.11 +/- 3.25 micrograms-h/ml vs 31.65 +/- 7.94 micrograms-h/ml respectively). Also, the sulindac sulfide AUC decreased (p < 0.05) to 7.26 +/- 4.37 micrograms-h/ml coadministration of both drugs compared to 44.69 ...
Tritium-labeled prednisolone sodium succinate was administered IV to 4 healthy, awake, nonsplenec... more Tritium-labeled prednisolone sodium succinate was administered IV to 4 healthy, awake, nonsplenectomized dogs. The concentration of prednisolone and its metabolites in the plasma were measured for 10 hours. Forty-one percent of the blood volume of these dogs was removed, and plasma prednisolone was measured again. The data before and after hemorrhage were fitted to a 2-compartment open model. From plasma profiles, a rapid distributional phase, followed by a slower phase, was observed in control and shock groups. Volume of the central compartment of prednisolone before and after hemorrhage was 165 ml/kg of body weight and 110 ml/kg, respectively; and the difference was significant (P less than 0.05). The rate of total body clearance of prednisolone before and after hemorrhage was 3.96 ml/min/kg and 2.53 ml/min/kg, respectively; the difference was significant. The mean plasma half-lives for prednisolone sodium succinate and its metabolites, before and after hemorrhage, were 166 and 19...
Predictions of free (unbound) serum phenytoin concentration by three methods were compared with r... more Predictions of free (unbound) serum phenytoin concentration by three methods were compared with results obtained by the Abbott TDx Free Phenytoin ultrafiltration and fluorescence-polarization immunoassay technique. Data were obtained for hospitalized adults who had been receiving phenytoin for at least five days and were free of renal or hepatic disease. Total phenytoin concentration was determined, and free phenytoin concentration was measured in ultrafiltrate at 25 degrees C. For each patient, measured concentrations of total phenytoin and albumin were used to predict free phenytoin concentrations by the Gugler method, the Sheiner-Tozer nomogram, and the Sheiner-Tozer equation. Mean measured percentages of free phenytoin were 17.79%, 12.13%, and 8.73%, respectively, for patients with albumin concentrations of less than 2 g/dL (n = 5), 2-3 g/dL (n = 18), and greater than 3 g/dL (n = 26). There was a strong correlation between actual and predicted free phenytoin concentrations for e...
Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of bo... more Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive days. Seventeen venous blood samples were collected from each horse after the single dose study and again after the last dose on day 42. Plasma phenobarbital concentration was determined by use of a fluorescence assay validated for horses. Additional blood samples (n = 11) were collected on days 8 and 25 to determine peak and trough concentrations, as well as total body clearance. Phenobarbital disposition followed a one-compartment model. Mean kinetic variables after single and repeated orally administered doses (42 days) were: elimination half-life = 24.2 +/- 4.7 and 11.2 +/- 2.3 hours, volume of distribution = 0.960 +/- 0.060 and 0.914 +/- 0.119 L/kg, and clearance = 28.2 +/- 5.1 and 57.3 +/- 9.6 ml/h/kg, respectively. Results indicated that significant (P less than 0.05) difference in half-life and oral clearance ex...
An improved liquid chromatographic procedure is described for the quantitative determination of s... more An improved liquid chromatographic procedure is described for the quantitative determination of sulindac, sulindac sulfone, and sulindac sulfide from serum. The procedure makes use of acetonitrile extraction of the compounds of interest from acidified serum samples. Under these conditions extraction efficiencies in the 85 percent range are obtained for each of the compounds. The liquid chromatographic separation of the compounds of interest and the internal standard (indomethacin) is accomplished in an isocratic elution procedure using a nitrile (CN) stationary phase. The HPLC separation procedure is completed in less than 10 minutes, giving excellent resolution and peak shape.
Clinical and Experimental Pharmacology and Physiology, 1981
1. Digoxin was associated into phosphotidylcholine liposomes at concentrations of 28-33 mol% in H... more 1. Digoxin was associated into phosphotidylcholine liposomes at concentrations of 28-33 mol% in Hank&#39;s Buffer, pH 7.4 at 28 degrees C. 2. Digoxin-liposomes (digoxin concentration 0.022 mg/kg per dog per day) administered intravenously in five adult male dogs attained therapeutic serum concentrations (0.7-3.0 ng/ml) beginning with day 1 of administration. 3. Digoxin serum concentrations obtained by intravenous digoxin-liposomes compared favorably with normal oral digoxin administration (0.022 mg/kg per dog per day) in all 5 dogs monitoring serum digoxin levels for 7 days showed no significant (P &lt; 0.05) differences in mean serum digoxin concentrations +/- s.e.m. on 6 of 7 days of treatments.
This study was undertaken to compare the susceptibility to inactivation of isepamicin with amikac... more This study was undertaken to compare the susceptibility to inactivation of isepamicin with amikacin and gentamicin when exposed to different beta-lactams, beta-lactamase inhibitors, and heparin. The aminoglycosides (5, 10, 20, and 50 micrograms/ml) were incubated in human serum with ampicillin, azlocillin, aztreonam, carbenicillin, ceftazidime, piperacillin, and ticarcillin (100 and 600 micrograms/ml) and with clavulanate, cilastatin, 1:1 imipenemcilastatin, oxacillin, and sulbactam (20 and 120 micrograms/ml) for 48 h at 37 degrees C. Aminoglycoside concentrations were measured by fluorescence polarization immunoassay (FPI) after 0, 8, and 48 h of incubation and by radial diffusion bioassay after 48 h of incubation. Each of the three aminoglycosides was also added to whole blood containing either heparin (100 U/ml) or 0.5% EDTA as a control and assayed after 6 h by FPI. The degree of inactivation of isepamicin by the beta-lactams was significantly less than that by amikacin (P less ...
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