Pharmacokinetics and disposition of the lipid-lowering drug acifran in normal subjects and in patients with renal failure.

The pharmacokinetics and metabolic fate of the antihyperlipidemic drug acifran were assessed after a single oral dose of the 14C-labeled drug to healthy male volunteers. Peak serum acifran and radioactivity concentrations were attained 1 to 2 hours after dosing, and the drug was eliminated with a half-life of 1.6 hours. Virtually all of the recovered dose was excreted in the urine. All of the serum and urinary radioactivity was caused by unconjugated acifran. In patients with moderate chronic renal failure, the binding of acifran to plasma proteins was decreased, and the plasma concentrations of total and unbound drug were greater than those of healthy subjects. Renal failure substantially reduced the plasma and renal clearance of total and particularly of unbound acifran, moderately reduced its volume of distribution, and increased its elimination half-life from 1.4 to 1.7 hours to 5.7 hours. The results show that acifran is very well absorbed, is rapidly eliminated, is excreted in the urine, and does not undergo any detectable biotransformation in healthy human subjects.

Bioavailability studies with etodolac in dogs and man.

The effects of formulation, particle size, coadministration of food, antacids, or antiulcer agents on the bioavailability of etodolac (ULTRADOL, 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid), a novel non-steroidal anti-inflammatory agent, have been evaluated in dogs and man. The effects of dosage regimen and/or repetitive dosing on bioavailability were also determined. In man, capsule and tablet dosage forms containing micronized etodolac were shown to have a bioavailability (AUC) equal to that of the reference etodolac solution. Etodolac from tablets and capsules was rapidly absorbed since only minor decreases in Cmax and increases in tmax were observed compared to the etodolac solution. In a comparison of regular and micronized etodolac dosage forms, both in dogs and man, similar findings, i.e. no change in AUC but small parallel changes in Cmax and tmax, were noted. Administration of etodolac with food had no effect on etodolac bioavailability in dogs but tended to cause a delay in its absorption. Coadministration of an antacid, magaldrate, or the antiulcer agent, sucralfate, had no effect on the bioavailability of etodolac in dogs, although with the latter, a significant reduction in Cmax was noted. In man, etodolac may be administered as a single bolus dose or in divided (b.i.d.) doses without any loss in bioavailability. With either regimen, on repeat administration for 7 days, no etodolac accumulation was noted.

Sensitive high-performance liquid chromatographic method for the determination of etodolac in serum.

A sensitive high-performance liquid chromatographic method for the determination of etodolac in serum was developed. The limit of detection was 0.2 microgram/ml. The specificity of the method was demonstrated by the lack of response obtained with a variety of control sera, sera spiked with etodolac congeners, and sera obtained from rats treated with a variety of other drugs.

Medrogestone: analysis in serum by high-pressure liquid chromatography.

A method for the determination of 6,17-dimethylpregna-4,6-diene-3,20-dione (medrogestone) in serum is described using high-pressure liquid chromatography with UV detection. Interfering substances in human or dog serum blanks were removed selectively by reaction with oxalyl chloride followed by an aqueous alkaline borate "wash" of the extract. The method is specific for medrogestone and, based on 5 ml serum, has a limit of detection of 2 ng/ml.

A high pressure liquid chromatographic determination of p-chlorophenoxyisobutyric acid and its comparison to a GLC and an ultra violet spectrophotometric method.

A rapid and reliable method for the determination of clofibric acid in serum using high pressure liquid chromatography has been elaborated and compared to a GLC and UV spectophotometric procedure. The limit of detection of the method is 0.3 micrograms/ml.

A sensitive method for the determination of hydrochlorothiazide in serum by high pressure liquid chromatography.

A high pressure liquid chromatographic method for the determination of hydrochlorothiazide in serum has been elaborated and verified in a blood level study in normal individuals given a single oral dose of 50 mg hydrochlorothiazide. Based on 5 ml of serum, the limit of detection of the method is 2 ng/ml.

An automated method for the analysis of nicotinic acid in serum.

Rational antihyperlipemic therapy based on the use of nicotinic acid and its derivatives and/or combinations demands a rapid and reliable method for monitoring nicotinic acid blood levels. To this end, an automated colorimetric method for the analysis of nicotinic acid in serum has been elaborated. For serum from rats, dogs and man given p.o. nicotinic acid or 3-pyridine methanol, the method is greater than 90% specific for nicotinic acid. The limit detection for nicotinic acid is 2 microgram/ml based on 0.15 ml of serum or 0.3 microgram/ml based on 1.5 ml of serum.

A method for the analysis of chlorhexidine in serum.

A colorimetric method for the determination of chlorhexidine in serum or plasma has been elaborated; the limit of detection of the method is 25 ng/ml, based on 10 ml of serum or plasma.