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Biomedical subjects

J G Wagner

Publications and source records attributed to J G Wagner.

At least 19 recordsLinked to original sources
PubMed1979

Rectal and oral absorption of methylprednisolone acetate.

Rectal absorption of methylprednisolone acetate and oral absorption of methylprednisolone and methylprednisolone acetate were investigated in a single-dose 3-way crossover study of 12 normal male volunteers. The median value of bioavailability (relative to oral dose) of methylprednisolone acetate based on unchanged methylprednisolone plasma levels was 14.2% after rectal administration, suggesting that the drug exerts its therapeutic effect topically rather than systemically. In contrast, the median of total radioactivity in urine (as a percentage of rectal dose) was 34.3% (range, 4.52% to 58.8%), suggesting partial bacterial metabolism in the rectum prior to absorption. Mean bioavailability (relative to oral administration of methylprednisolone acetate) of methylprednisolone after oral administration was 89.9%, indicating somewhat better systemic availability of the ester than the alcohol. The average apparent elimination rate constant for methylprednisolone after oral administration of both ester and alcohol was 0.290 hr-1, corresponding to a half-life of 2.39 hr.

Absorption↗
PubMed1979

A method to predict infinity values for biexponential processes.

An equation is presented which allows infinity values for biexponential processes to be predicted in the early nonlinear phase when samples are taken at equal time intervals. This equation is independent of the value or ratio of the rate constants involved in the process. However, this method is very sensitive to noise normally associated with urine data.

Digoxin↗
PubMed1979

Pharmacokinetics of propranolol in the cat and comparisons with humans and three other species.

The aims of this study were to describe the pharmacokinetics of propranolol in the cat, to compare pharmacokinetic parameters for propranolol in the cat with those of four other species and to apply the two-step infusion method of Wagner (Clin. Pharmacol. Ther. 16, 691-700, 1974) in order to attain a rapid steady-state level for propranolol in plasma. Seven healthy adult cats received propranolol either as an I.V. bolus or by the two-step I.V. infusion method. The latter method was very effective in rapidly attaining and maintaining steady-state plasma propranolol levels. Pharmacokinetic parameters for propranolol in the cat are as follows: plasma clearance, 31.3 ml/(kg x min); volume of distribution, 1.57 L/kg; elimination half-life, 35 min. When compared with other species, the order of plasma clearances for propranolol were: rat greater than dog greater than cat greater than man greater than monkey. A plot of total area under the plasma propranolol concentration-time curve versus dose was not linear at the lower doses, but was linear at doses greater than 0.242 mg/kg.

Animals↗
PubMed1979

Errors in interpretation of data from equilibrium dialysis protein binding experiments.

In equilibrium dialysis protein binding experiments, the fraction of free or bound drug determined at equilibrium by dialysis of a patient plasma sample does not correspond to the drug concentration in the initial plasma sample, but to the drug concentration inside the plasma compartment of the dialysis apparatus at equilibrium. That fraction of free or bound drug corresponds to a lower total drug concentration than that in the initial plasma sample because of loss of drug due to passage of free drug into the buffer compartment in the equilibrium dialysis experiment. The magnitude of the difference between the initial drug concentration and the equilibrium drug concentration depends on the extent of drug binding and experimental conditions. If the initial total drug concentration in the plasma or serum sample as well as the fraction of drug bound at equilibrium as determined by radiotracer methods are known, then, using methods given in the text, the equilibrium drug concentration, the binding parameters corresponding to equilibrium conditions, and the free drug concentration in the initial plasma sample may be estimated.

Blood Proteins↗
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↗
PubMed1978

Pharmacokinetics of digoxin in the cat and comparisons with man and the dog.

Digoxin doses of 14.3, 5.72 or 1.43 mcg/kg were administered to 8 cats and the plasma digoxin concentrations (concns) were measured as a function of time for 96 hr. Pharmacokinetic linearity was evidenced by: (1) mean plasma clearance (Clp) of 4.05 ml/(kg x min) with a coefficient of variation of 34.6% and a range of 2.69-6.71; (2) linear relationship between total area under the plasma concn-time curve and the administered dose. Further evidence for linearity was the lack of dose-dependence of apparent elimination half-life (beta). The volume of distribution and beta for cats were respectively (mean +/- s.d.) 20.4 +/- 5.35 L/kg and 0.0120 +/- 0.0030 hr-1. Results from cats were compared with literature data for dogs and man. The order of Clp in units of ml/(kg x min) were: infant greater than dog greater than cat greater than adult man.

Adult↗
PubMed1978

Preliminary in vitro and in vivo investigations on methylprednisolone and its acetate.

Sodium fluoride (6--8 mg/ml) inhibits hydrolysis of methylprednisolone acetate to methylprednisolone. An HPLC method for simultaneous determination of hydrocortisone, methylprednisolone and methylprednisolone acetate in plasma is presented. Analysis of plasma samples (containing NaF) for methylprednisolone acetate shows no significant change in concentration over extended periods of storage at -20 degrees C. In vitro hydrolysis of methylprednisolone acetate at 37 degrees C in human whole blood is rapid (average t1/2 = 19 min). In one cat, the bioavailabilities of methylprednisolone acetate rectally was 13% and of methylprednisolone (alcohol) rectally was 26%, relative to intravenous administration of methylprednisolone. In the same cat, the bioavailabilities of methylprednisolone acetate orally was 93% and of methylprednisolone was 82%, relative to intravenous administration of methylprednisolone. All samples collected after oral administration of methylprednisolone acetate to a human subject were found to contain only methylprednisolone (alcohol) indicating hydrolysis of the drug during absorption through the gastrointestinal membrane and/or in the liver. If the ester had the same half-life in blood in vivo as measured in vitro, it would have been measurable in plasma.

Acetates↗
PubMed1977

Circadian rhythm of urinary pH in man with and without chronic antacid administration.

In normal human volunteers, when urinary pH was plotted versus time, the circadian sine-wave type curve was not altered by chronic administration of a commercially available suspension containing a mixture of magnesium and aluminum hydroxides, although the antacid perturbed the entire curve in a more alkaline direction. A single dose of the antacid had little effect on urinary pH. There was a highly significant linear relationship between the change in hydrogen ion concentration during chronic antacid treatment and the initial control urinary hydrogen ion concentration, but there was no significant correlation between change in urinary pH and initial control urinary pH as has been previously reported. The above results were based on the evaluation of the hydrogen ion concentrations of 1562 separate urine samples collected from 24 normal subjects in a three treatment crossover study. It is recommended that: (1) research studies involving drug-drug interactions with antacids be designed to consider the effect of the antacid on the circadian rhythm of urinary pH, and (2) pH values not be averaged as commonly reported in the literature, but rather the pH values be converted to hydrogen ion concentrations before statistical analysis.

Adult↗
PubMed1977

Error dependent on renal function when monoexponential equation assumed. Serum clearances of 125I-iothalamate and 131I-o-iodohippurate.

An example from the literature has been used to demonstrate errors involved in calculating drug clearance by inappropriate use of the apparent drug distribution volume Vdext. The Vdext is always an overestimate of the true volume of distribution in a multicompartment system, and the degree of overestimation in using it to calculate clearance for such a system will increase as renal function increases. Drug dosages calculated on the basis of overestimated clearance values may give rise to overdosage in normal individuals, or therapeutic failure in severely uremic patients. Problems associated with the use of an oversimplified pharmacokinetic model for clearance calculations are discussed, together with the concept of model-independent calculations.

Humans↗