Yukiya Saitoh

Estimation of plasma unbound phenobarbital concentration by using mixed saliva.

Summary: Relationships among plasma total (Ct), plasma protein unbound (Cf) and mixed salivary (Cs) concentrations of phenobarbital (PB) were studied in 29 epileptic patients. A highly significant correlation was observed between C, and Cf. Although a significant correlation was observed between Cf and Cs, Cs/Cf ratio was only 0.63. When Cs was corrected by using pKa (7.41) and pH of saliva to estimate free PB concentration (Cest f), a highly significant correlation was obtained between Cf and Cestf, and Cest f/Cf ratio was 0.96. The temporal course of Cest f obtained from Cs after an oral single dose of 50 mg PB in a healthy adult male volunteer was approximated as a triexponential equation. The peak time was 2 hr after ingestion and apparent half‐life was 66 hr. The prediction of minimum concentrations at steady state on the basis of these parameters corresponded well with actually obtained Cest f following repetitive administration of PB.

Quantitative determination of furosemide in plasma, plasma water, urine and ascites fluid by high-performance liquid chromatography

A high-performance liquid chromatographic method using spectrofluorometric detection is described for the determination of furosemide in plasma, plasma water, urine and ascites fluid. The extraction procedure decreases interference from endogenous substances. The detection limit of furosemide is 10 ng in 0.5 ml of biological sample. The method is sufficiently sensitive for pharmacokinetic study of furosemide with normal subjects and patients with liver cirrhosis and/or renal disease after oral administration of furosemide in a retard capsule, and for study of protein binding of furosemide in patients with various diseases.

Determination of ambenonium in biological samples by reversed-phase ion-pair liquid chromatography.

A sensitive and selective analytical method for the determination of ambenonium ion in biological samples is described. The procedure involves ion-pair extraction of the drug, followed by reversed-phase ion-pair chromatographic analysis with ultraviolet detection at 217 nm. The detection limits at a signal-to-noise ratio of 5 were 100 pmol/ml using 0.2 ml of plasma and bile, 250 pmol/ml using 0.2 ml of urine and 200 pmol/g using 1 ml of tissue homogenates containing 0.1 g/ml of each tissue. This assay procedure was used to study the pharmacokinetics of ambenonium ion after intravenous administration in rats.

Determination of pemoline in plasma, urine and tissues by reversed-phase high-performance liquid chromatography

A simple and selective high-performance liquid chromatographic method with ultraviolet detection at 215 nm for the determination for pemoline in rat plasma, urine and tissues is described. Pemoline in the samples was extracted with methylene chloride at pH 10 and the organic phase was evaporated after adding 5-methyl-5-phenylhydantoin used as an internal standard. Pemoline and the internal standard were separated on a Kaseisorb LC C8-60-5 reversed-phase column. The limits of determination of pemoline in 0.1-0.2 ml of plasma, urine and tissue homogenates were 2, 100 and 20 ng, respectively. The method should be useful for studies of the pharmacokinetics and distribution of pemoline in small animals.

Quantitative determination of propranolol in plasma and plasma water from normal subjects and patients with angina pectoris by high-performance liquid chromatography

A precise and sensitive high-performance liquid chromatographic method using a column packed with porous polystyrene gel is described for the determination of propranolol in plasma and plasma water from normal subjects and patients with angina pectoris. Propranolol in the samples was extracted with an n-heptane-isoamylalcohol (98.5:1.5) mixture after addition of penbutolol used as an internal standard. The extracts were chromatographed and detected with a spectrofluorophotometer. The quantitative limit of propranolol was 1 ng using 1 ml of plasma or 0.5 ml of plasma water. The present method should be useful for monitoring propranolol concentrations in plasma and plasma water during drug therapy and for pharmacokinetic study of propranolol.

Clinical Application of Immunoprecipitation Inhibition Technique for Determination of Carbamazepine and Theophylline in Serum

The immunoprecipitation inhibition technique (i-PiT method) was used in the clinical application to determine the concentration of carbamazepine (CBZ) and theophylline (TH) in serum. Each coefficient of variation for the 3 levels of CBZ or TH was less than 9% within-run and betweenrun. The serum CBZ concentration determined by the i-PiT method was compared with that determined by high-performance liquid chromatography (HPLC). The correlation coefficient was 0.990, but serum CBZ concentration determined by the i-PiT method was about 15% higher than that determined by HPLC because of the cross reactivity in carbamazepine-10, 11-epoxide. Other antiepileptic drugs, such as phenytoin, phenobarbital and primidone, did not interfere with the i-PiT method under therapeutic condition. The serum TH concentration determined by the i-PiT method was compared with that determined by HPLC. There was good agreement between the i-PiT method and HPLC results, where the correlation coefficient was 0.994. The metabolites of TH, such as caffeine and theobromine, did not interfere with the i-PiT method under therapeutic conditions. Therefore, the i-PiT method may be useful for the serum level monitoring of patients undergoing TH therapy.

A Work Sampling Study of Staff Members in a Hospital Pharmacy Drug Information Center

A work sampling method was applied to provide a description of the tasks performed by staff members in the hospital pharmacy drug information center of the University of Tokyo. A total of 1090 observations were recorded during 13 days in 3-week period on each of the three pharmacists and a part-timer. Productive time was 78% of the total time. The collection and distribution of drug information occupied 60% and 36% of productive time, respectively.

Interaction between Plasma Phenytoin and Phenobarbital Concentrations in Epileptic Patients

Interaction between phenytoin (PHT) and phenobarbital( PB) in epileptic patients was studied by simultaneously determining their plasma concentrations. The subjects of study were 158 adult epileptic outpatients at the Department of Neuropsychiatry, Tokyo University Hospital, and at Fujisawa Hospital. Most of the patients suffered bilateral generalized convulsions, and were maintained at steady state concentrations of PHT and/or PB. Patients consisted of PHT group (51 patients with PHT only), PB group (6 patients with PB only) and PHT + PB group (101 patients). Plasma PHT and PB concentrations were determined by the UV method.* In both PHT and PHT + PB groups the dose-level relationships of PHT showed Michaelis-Menten type curves. In the PHT + PB group the dose-level relationship of PHT was not different from that of the PHT group when plasma PB concentrations were less than 20pg/ml. When PB concentrations were higher than 20 pg/ml, and when the PHT doses were higher than about 4.5mglkg per day, the PHT concentrations of the PHT + PB group showed a decrease when compared to the PHT group. This finding suggests that PB either accelerates the metabolism of PHT in the liver or inhibits the absorption of PHT