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Biomedical subjects

R D Shaffer

Publications and source records attributed to R D Shaffer.

At least 19 recordsLinked to original sources
PubMed1990

Performance of diltiazem tablet and multiparticulate osmotic formulations in the dog.

The in vivo performance of two extended-release (ER) osmotic formulations of diltiazem were evaluated in the beagle dog. Both ER formulations had similar bioavailabilities (F) as the diltiazem solution. Although F was somewhat variable following ER administration, this variability may be related to the drug entity since intra- and interanimal variability of orally administered diltiazem solutions was substantial. Deconvolution of the ER plasma diltiazem data with absorption data from the orally administered diltiazem solutions provided an estimate of the in vivo drug release from the ER formulations. The two ER formulations, designed with different in vitro release profiles, reflected these differences in vivo, with nearly identical respective in vivo and in vitro release profiles.

Absorption↗
PubMed1983

Fulminant hepatitis associated with disulfiram. Report of a case.

Disulfiram is used commonly as reinforcement in the treatment of chronic alcoholism. Although the drug is generally considered safe, there are reports of side effects including psychosis and hepatitis. We report a case of fatal fulminant hepatitis caused by the use of disulfiram in a man with previously normal hepatocellular function.

Acute Disease↗
PubMed1982

The use of N,N-diethyl-m-toluamide to enhance dermal and transdermal delivery of drugs.

A dermal penetration enhancer has been found which improves the dermal delivery of a wide variety of drugs and at the same time has a history of low toxicity for human dermal application. N,N-Diethyl-m-toluamide (I) has been shown to improve the delivery of many drugs through hairless mouse skin in an in vitro diffusion cell model. A topically applied steroid, hydrocortisone, has been used to demonstrate the in vivo effectiveness of I on human skin. The degree of pallor produced on human skin by the corticosteroids was used as a measure of the relative delivery of hydrocortisone from formulations with and without I.

Animals↗
PubMed1979

GLC determination of whole blood antimalarial concentrations.

An assay was developed for determining mefloquine (quinolinemethanol) and pyridinemethanol derivative concentrations in whole blood. The method involved ion-pair extraction or usual solvent extraction for drug recovery from whole blood followed by trimethylsilylation. The silylated compounds were then submitted to GLC with electron-capture or flame-ionization detection. Mass spectrometry combined with GLC of the trimethylsilyl derivatives indicated that substitution of one trimethylsilyl group had occurred on the hydroxyl group. A phenyl methyl silicone column with temperature programming separated the drugs from normal blood extracts. The determination limit was 10 ng/ml of whole blood when an electron-capture detector was used with ion-pair extraction. Quantitation was achieved by using one antimalarial as an internal standard for the assay of the other. The utility of the present method was demonstrated by following the whole blood level time course after a single oral 250-mg tablet in beagle dogs.

Animals↗
PubMed1978

Kinetics of digoxin stability in aqueous solution.

Digoxin hydrolysis was studied as a function of pH. Conversion of digoxin to digoxigenin was followed by high-pressure liquid chromatography and shown to proceed by the initial loss of one, two, or three sugars. The hydrolysis rate was directly proportional to parent drug concentration and hydrogen-ion activity. The individual hydrolysis rate constants of digoxin, digoxigenin bisdigitoxoside, and digoxigenin monodigitoxoside were determined by a simplex fitting procedure. Data are presented suggesting that at least some variation in the bioavailability of orally administered digoxin arises from observed variations in gastric pH; these variations influence the extent to which hydrolysis occurs and, thus, modify the composition of digoxin species available for absorption.

Chemical Phenomena↗
PubMed1977

Endoscopic electrosurgical papillotomy and manometry in biliary tract disease.

Endoscopic papillotomy was performed in 13 patients after cholecystectomy for retained or recurrent common bile duct calculi (11 patients) and a clinical picture suggesting papillary stenosis (two patients). Following endoscopic papillotomy, ten of the 11 patients spontaneously passed common bile duct (CBD) stones verified on repeated endoscopic retrograde cholangiopancreatography (ERCP) study. One patient failed to pass a large CBD calculus; one patient experienced cholangitis three months after in inadequate papillotomy and required operative intervention. Endoscopic papillotomy substantially decreased the pressure gradient existing between the CBD and the duodenum in all five patients studied with ERCP manometry. Endoscopic papillotomy is a relatively safe and effective procedure for postcholecystectomy patients with retained or recurrent CBD stones. The majority of CBD stones will pass spontaneously if the papillotomy is adequate.

Ampulla of Vater↗
PubMed1977

Quantitation of the antimalarial agent, mefloquine, in blood, plasma, and urine using high-pressure liquid chromatography.

Sensitive and specific assays are described for the quantitation of mefloquine in whole blood, plasma, and urine specimens using high-pressure liquid chromatography. Specimens were extracted with ethyl acetate and concentrated before chromatography. Whole blood and plasma extracts were chromatographed on a polar bonded phase partitioning column, and urine extracts were chromatographed on a bonded reversed-phase partitioning column. The sensitivity of the assays for mefloquine was 0.05 microgram/ml of whole blood or plasma and 0.25 microgram/ml of urine using 5-ml samples. The assays are suitable for studying mefloquine pharmacokinetics in humans.

Adult↗
PubMed1975

Rational development of a soluble prodrug of a cytotoxic nucleoside: preparation and properties of arabinosyladenine 5'-formate.

The 5'-O-formate ester of arabinosyladenine was synthesized and shown to be suitable as a water-soluble prodrug, being at least 60 times more soluble than the parent cytotoxic nucleoside. This increased solubility was ascribed to a decrease in intermolecular interaction in the crystalline state, as evidenced by an similar 90 degrees lower melting point for the ester relative to the parent compound. The prodrug reverted to the parent compound in aqueous solution, its pH-rate profile being V-shaped with maximum stability at a pH similar 4.2, corresponding to a half-life of about 10 days. The rate of hydrolysis of the prodrug at 37degrees in 91% human serum and 91% whole blood was studied. At an initial concentration of 0.4 mg of prodrug/ml of 91% whole blood, reversion to arabinosyladenine appeared to be essentially complete in about 15 min. The prodrug did not appear to be subject to enzymatic deamination. This feature, together with the good solubility of the prodrug, makes possible the effective formulation of arabinosyladenine for intravenous purposes. The rationale involved in the general design of a prodrug and the specific considerations necessitated in the case of adenine arabinoside are discussed.

Animals↗