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Biomedical subjects

R G Stoll

Publications and source records attributed to R G Stoll.

At least 19 recordsLinked to original sources
PubMed1982

Pharmacokinetics of hydroxyethyl starch in normal subjects.

To determine the elimination of high-molecular-weight hydroxyethyl starch (HES, Mw 450,000) in normal subjects, ten volunteers were given 500 ml 6% HES solution by intravenous infusion, and serial blood and urine samples were collected for nonglucose total carbohydrate determination. On the average, 46 and 64 per cent of the dose was excreted in the urine within two and eight days, respectively. The plasma concentration declined rapidly during the first week after infusion. The average terminal half-life was 17 days during the first 42 days, which accounted for elimination of about 90 per cent of the dose. The remainder was eliminated with a terminal half-life of 48 days determined between days 42 and 83 of the study. As expected, the infusion of HES resulted in plasma volume expansion over a 48-hour period during which time levels of nonglucose carbohydrates were above 3.5 mg/ml. HES is metabolized by alpha-amylase in the body. During the first 48 hours after infusion of HES, plasma alpha-amylase activity was significantly increased over control. Concomitantly, alpha-amylase activity in urine was also elevated but not significantly so.

Adult↗
PubMed1981

The assessment of the intrasubject variability in digoxin absorption in man from two oral dosage forms.

The reproducibility of drug absorption within a given subject as well as the evaluation of bioavailability of two digoxin dosage forms were studied. The data showed (a) a higher initial plasma digoxin concentration after the soft elastic gelatin (SEG) capsule; (b) a more irregular absorption after the tablet; (c) on the average, the coefficients of variation of individual plasma concentrations were lower after the capsule; and (d) for the capsule, the intrasubject variations of the peak plasma concentrations, time of peak, area under plasma concentrations-versus-time curve (AUC), and amount digoxin excreted in urine (Ae) were on the average 60 per cent of the variations in the tablet parameters. The ratios of AUC and Ae for capsule/tablet were essentially unity, indicating that the amount digoxin absorbed from the 0.4-mg digoxin SEG capsule is identical to that from a 0.5-mg standard reference tablet.

Absorption↗
PubMed1980

Evaluation of sustained-action chlorpheniramine-pseudoephedrine dosage form in humans.

This investigation compared the bioavailability of chlorpheniramine and pseudoephedrine from a sustained-action capsule and a combination of two reference standard tablets in 24 normal human subjects. The capsule contained 8 mg of chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride, and the tablets each contained half of the amount of the chlorpheniramine or pseudoephedrine in the capsule. Because the capsule was a combination product, a new study design had to be developed to accommodate steady-state conditions for both drugs. Each subject received the capsule (every 12 hr) and the combination of the reference tablets (every 6 hr) for 8 days according to a two-way crossover design. Serial blood and urine samples were taken during the entire study. Plasma and urine samples were assayed for chlorpheniramine and pseudoephedrine by sensitive and specific high-pressure liquid chromatographic or GLC methods. There were no significant differences in the plasma concentration profiles of chlorpheniramine and pseudoephedrine at all times, except when the capsule developed peaks or the tablets developed nadirs. The highest mean peak plasma concentrations for the capsule and the tablets were 38.7 and 32.9 ng of chlorpheniramine/,ml and 525 and 515 ng of pseudoephedrine/ml, respectively. The mean biological half-lives of chlorpheniramine and pseudoephedrine were 21.6 and 8.0 hr, respectively. The AUC and unchanged drug excreted in urine, after a single dose and at steady state, showed that the sustained-action capsule (given every 12 hr) and the reference standard tablets (given every 6 hr) were bioequivalent.

Adult↗
PubMed1980

Nitroglycerin compatibility with intravenous fluid filters, containers, and administration sets.

The effect of intravenous filters, containers and administration sets on nitroglycerin potency was studied. Solutions of nitroglycerin (50 and 100 microgram/ml) in water for injection, in 5% dextrose injection and in 0.9% sodium chloride injection were prepared. The concentration of these solutions was measured after (1) filtration through a 0.2-micron filter, (2) storage in glass and plastic containers and (3) administration through eight i.v. administration sets. Filters decreased nitroglycerin concentration by 2--55%. Nitroglycerin concentration was not changed after storage for 48 hours in glass bottles. In plastic i.v. bags, concentration decreases were substantial and related to surface contact area and storage temperature. The i.v. administration sets caused immediate, substantial decreases in nitroglycerin concentration that were a function of drip rate, surface area, length of exposure to tubing, and tubing materials. The study suggests that concentrations of nitroglycerin solutions could be reduced by as much as 80% when filtered, placed in a plastic i.v. bag and given through an i.v. administration set.

Drug Packaging↗
PubMed1980

Endogenous serum testosterone in males after different doses and routes of administration of medroxyprogesterone acetate.

The effects of different doses and routes of administration (oral and IM) of medroxyprogesterone acetate on endogenous testosterone secretion were studied in healthy male volunteers. There were three treatment groups. Serum testosterone levels, measured by radioimmunoassay before, during and after different doses of medroxyprogesterone acetate, were significantly lowered (p < 0.05) in these subjects. A tendency to return toward pretreatment values was noted within three to six weeks after the last dose of medroxyprogesterone acetate. The IM route of administration suppressed the testosterone levels for the longest period of time. No indication of drug-induced toxicity, as judged by vital signs, systemic side effects, standard laboratory evaluations and some special clinical evaluations, was found during treatment or in the period immediately following the course of therapy. No serious or untoward side effects were encountered.

Administration, Oral↗
PubMed1979

Urinary excretion of chlorpheniramine and pseudoephedrine in humans.

A specific high-pressure liquid chromatographic method for the determination of chlorpheniramine and pseudoephedrine in urine was developed and applied in a urinary excretion study of normal healthy subjects who received a sustained-release dosage form contianing 8 mgof chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride. Five subjects received one dose on Day 1, followed by multiple dosing every 12 hr for 7 days without ammonium chloride administration. Four subjects received one dose of the sustained-release dosage form together with ammonium chloride. Urine samples were collected during the 1st day and at steady state. The method is specific and simultaneously determines choorpheniramine, two metabolites (mono- and di-desmethylchlorpheniramine), pseudoephedrine, and norpseudoephedrine. The assay recovery was less than 97% (0.06-3 microgram/ml) for chlorpheniramine maleate and less than 98% (1.5-75 microgram/ml) for pseudoephedrine hydrochloride. Excretion of chlorpheniramine and its two metabolites in urine was enhanced after ammonium chloride administration. At steady state, a change in urine pH from 5.69 to 6.46 resulted in more than a 25% decrease in chlorpheniramine and monodesmethylchlorpheniramine excretion. In spite of expected changes in its biological half-life, the overall amount of unchanged pseudoephedrine excreted in urine was not affected by urine pH, presumably because it is primarily excreted in urine as intact drug.

Chlorpheniramine↗
PubMed1978

Comparison of in vitro dissolution and in vivo bioavailability of methaqualone tablets in humans.

Two methaqualone tablets that exhibited different in vitro dissolution rates were administered to 11 normal healthy male volunteers. Serial blood samples were withdrawn following administration of each tablet, and plasma methaqualone concentrations were determined by an established spectrophotofluormetric assay. Both tablets produced virtually identical plasma concentration versus time profiles in humans, and no statistically significant differences in either the rate or extent of drug absorbed were detected. The results indicate that there is no correlation between in vivo bioavailability and the modified NF in vitro dissolution test used.

Adult↗
PubMed1978

Influence of kaolin--pectin suspension on digoxin bioavailability.

The effect of a kaolin--pectin suspension on the bioavailability of orally administered digoxin was evaluated when both drugs were given concomitantly and when their time of administration was separated by 2 hr. Coadministration of the antidiarrheal with the cardiac glycoside delayed absorption of the latter and, at the same time, decreased by 62% the amount of drug absorbed. Intersubject variation in digoxin bioavailability also was increased more than twofold. When the kaolin--pectin suspension was given 2 hr before the cardiac glycoside, the digoxin absorption rate was not affected, although its relative extent of absorption was reduced by about 20%. In contrast, when the antidiarrheal was given 2 hr after digoxin, neither the rate nor the extent of absorption of the cardiac glycoside was perturbed. No change in the intersubject variability in digoxin bioavailability was noted whether the antidiarrheal was given 2 hr before or 2 hr after the cardiac glycoside.

Adult↗
PubMed1977

Generic propoxyphene: need for clinical bioavailability evaluation.

Plasma level data on two investigational capsule formulations of propoxyphene with similar physicochemical parameters demonstrate that the formulations have different in vivo bioavailabilities. The potential bioavailability problems with water-soluble drugs and the lack of correlation of in vitro and in vivo parameters for equivalent drug formulations are discussed.

Adult↗
PubMed1976

Clinical bioavaiability of nitrofurantoin--a case of bioinequivalence.

In a crossover study of the bioavailability of marketed nitrofurantoin tablets, there were significant differences in the urinary excretion of nitrofurantoin suggestive of bioavailability problems with this drug. Standard in vitro assessments of dissolution rate and disintegration time were not correlated with bioavailability and failed to detect 3 to 18 fold differences in the amount of nitrofurantoin absorbed. In fact, four lots, made by the same manufacturer had almost identical in vitro measurements (dissolution rate; distinegration time), yet two of these lots were only 6.6 and 26% as available as the reference nitrofurantoin product, and two others were comparatively available. The need for the development of an in vitro - in vivo correlation for control of lot to lot uniformity has clearly been demonstrated for nitrofurantoin. Such correlations must include tests other than those presently required.

Adult↗
PubMed1976

Intersubject variation of warfarin binding to protein in serum of normal subjects.

The protein binding of warfarin was determined in the serum of 18 normal adult subjects (8 males and 10 females). A statistically significant negative correlation between free fraction of warfarin and albumin concentration was found. The free fraction of warfarin in the serum of women was significantly larger than that in the serum of men, apparently due to the lower albumin concentration in the serum of women.

Adult↗
PubMed1975

Antibiotic batch certification and bioequivalence.

All antibiotics marketed in the United States must undergo batch certification by the Food and Drug Administration. It is often assumed that the different brands of a particular antibiotic that pass in vitro batch certification tests have equal in vivo bioavailability. The fallacy of this assumption is clearly supported for commercially available lots of tetracycline hydrochloride that had passed batch certification tests yet had different serial serum concentrations.

Administration, Oral↗