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Biomedical subjects

R V Tomlinson

Publications and source records attributed to R V Tomlinson.

15 recordsLinked to original sources
PubMed1992

Percutaneous absorption and metabolism of lonapalene in psoriatic skin.

The percutaneous absorption and metabolism of lonapalene (6-chloro-2,3-dimethoxynaphthalene-1,4-diol-diacetate; RS-43179), a topically effective 5-lipoxygenase inhibitor, has been measured in six subjects with stable plaque-type psoriasis of the lower extremities. Lonapalene readily penetrates psoriatic skin, is rapidly and completely metabolized, and is almost entirely excreted in the urine. Unexpectedly we observed a trend for thigh (T) plaque skin to be more permeable than lower leg (LL) plaque skin as measured by total absorption (T, 44.8 +/- 13.4%; LL, 24.9 +/- 12.6% applied dose excreted), peak plasma levels (T, 209 +/- 107; LL, 146 +/- 81 ng Eq/ml), and peak rate of urinary excretion (T, 591.7 +/- 112.2; LL, 318.4 +/- 143.9 micrograms Eq/hr). There were also differences in the metabolic profiles between the two sites as measured by the quantity and proportion of dealkylated and conjugated products excreted in the urine.

Administration, Cutaneous↗
PubMed1990

Pharmacokinetic and tissue residue characteristics of fenprostalene, a prostaglandin F2 alpha analog, in swine.

Fenprostalene, a prostaglandin F2 alpha analog, can be used to induce parturition in swine. As part of the approval process for that indication, pharmacokinetic characteristics of the absorption and elimination of fenprostalene and the depletion of drug residues from the principal edible tissues of swine were studied. Blood samples, urine, and feces were collected from 8 gilts (body weight, 95 +/- 1.7 kg) for up to 72 hours after a single dose of 0.5 mg of 13,14-[3H]-fenprostalene in polyethylene glycol-400 was administered SC. At intervals of 24, 48, 72, and 168 hours after dosing, 2 gilts each were killed, and samples of liver, kidney, muscle, and abdominal fat were obtained for analysis. The mean (+/- SEM) maximal concentration of fenprostalene radioequivalents in plasma (0.41 +/- 0.05 nanogram-equivalents/ml; n = 8) was observed at 12 hours and decreased biexponentially, with half-lives of approximately 8 hours and 9 days. Mean cumulative recovery (n = 4) of the administered dose by 72 hours was 61.2 +/- 5.9% in urine and 18.5 +/- 2.6% in feces. The highest tissue fenprostalene concentration was in kidneys and liver, probably reflecting the role of those organs in excreting fenprostalene. Rates of depletion of fenprostalene equivalents from the injection site, kidneys, and liver were comparable with those previously observed in cattle. The composition of residue in the liver of 2 gilts slaughtered 12 hours after SC administration of [3H]-fenprostalene was examined in a second study. Results suggested that approximately 4% of the total residue was pharmacologically potent fenprostalene or the carboxylic acid form of fenprostalene.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents↗
PubMed1985

Absorption and elimination of a prostaglandin F analog, fenprostalene, in lactating dairy cows.

Pharmacokinetic characteristics of the prostaglandin F2 alpha analog, fenprostalene, were studied in five lactating Holstein cows. Blood samples, milk, urine, and feces were collected for up to 7 d following a single subcutaneous injection of 1 mg of 13,14-hydrogen-3-fenprostalene in polyethylene glycol-400. The maximum concentration of tritium in plasma, observed 4 h after injection, equated to .17 ngeq/ml fenprostalene and declined with a fractional disappearance rate of .051 X h-1 to less than .04 ngeq/ml by 48 h. Likewise, milk contained .53 ngeq/ml fenprostalene at 4 h and the concentration declined with a fractional disappearance rate of .069 X h-1 to less than .03 ngeq/ml by 48 h. Milk was a very minor route of elimination of fenprostalene with only .46% of the injected dose recovered over a 7-d sampling. Recovery of tritium in urine accounted for 55% of the total dose and recovery in feces accounted for an additional 43%. Residues from fenprostalene at 7 d after injection were less than .1 ppb in all edible tissues. Differences in the molecular structure, formulation, and route of injection of fenprostalene resulted in a slower rate of absorption and elimination of this analog than previously reported for other prostaglandin products. Nonetheless, the percentage of the injected dose of fenprostalene secreted in milk was not increased appreciably, and no persistent tissue residues of fenprostalene were observed.

Abortifacient Agents↗
PubMed1984

Absorption, excretion and tissue residue in feedlot heifers injected with the synthetic prostaglandin, fenprostalene.

Preliminary studies on use of the synthetic prostaglandin, fenprostalene, as an abortifacient had indicated that maximum effectiveness was dependent upon slow delivery. Because both route of administration and formulation control delivery rates, the influences of intramuscular (im) vs subcutaneous (sc) injections, and aqueous acetate buffer (AAB) vs polyethylene glycol-400 (PEG) vehicles on the plasma concentration and urinary excretion of fenprostalene were compared. Feedlot heifers were administered 1 mg injections of [13,14-3H]-fenprostalene. Blood samples and total urine excretion were collected during the following 96 h. The maximum concentration of tritium in plasma occurred at 2 h for AAB-im (.90 ng eq/ml), PEG-im (.75 ng eq/ml) and AAB-sc (.64 ng eq/ml), and then declined throughout 24 h with t 1/2 values of 6.1, 9.4 and 9.2 h, respectively. The peak concentration from PEG-sc was lower (.37 ng eq/ml, P less than .05), observed later (4h, P less than .05) and declined more slowly following peak concentration (t 1/2 = 15.1 h, P less than .05). Consistent with delayed absorption, a smaller fraction (P less than .05) of the total radioactivity excreted in urine was recovered during the first 24 h after injection for PEG-sc (85%) than for PEG-im (95%), AAB-sc (97%) or AAB-im (99%). In a tissue distribution study, plasma, urine and fecal samples were collected and heifers were slaughtered at various times following sc injection of 1 mg of [3H] fenprostalene in PEG. Peak concentrations of tritium in plasma occurred between 4 and 8 h and declined with a t 1/2 of 15.2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents↗
PubMed1980

Manipulation of duration of action of a synthetic prostaglandin analogue (TPT) assessed in the pregnant beagle bitch.

Beagle bitches were treated on days 20-22 of pregnancy with TPT as an aqueous solution administered subcutaneously via a minipump at a rate of 10 micrograms per hour for either 24 (I) or 48 hours (II). Additional animals received a single subcutaneous injection of 200 micrograms of TPT as an aqueous solution (III) or dissolved in polyethylene glycol 400 (IV) or the methyl ester of TPT dissolved in polyethylene glycol 400 (V). The duration of action was assessed by the nadir in circulating progesterone levels. By this criterion the duration of action in the different groups ranked I=III<II=IV<V, the nadir occurring at 2, 3 and 3-4 days post treatment, respectively. Duration of action correlated with the incidence of abortion. Salivation, emesis and diarrhea or hypothermia side effects, previously noted for this agent, were not affected by the manipulations of duration of action.

Abortifacient Agents↗
PubMed1978

Cloprednol bioavailability in humans.

The bioavailability of cloprednol, a new systemic corticosteroid, was examined in a 12-subject crossover study in which two capsules, a tablet, and a solution were tested. Plasma was analyzed for cloprednol by a GLC-mass spectrometric method. The biological half-life, peak plasma concentration, peak time, plasma concentration at all sampling times, and plasma areas were evaluated for differences (p less than or equal to 0.05) in comparisons of pairs among the four formulations. An analysis of variance revealed that cloprednol was absorbed to the same extent from all formulations and rapidly cleared from the plasma with a half-life of 1.86 +/- 0.36 (SD) hr. All plasma profile parameters from the solid dose formulations were the same, demonstrating bioequivalence in both rate and extent of absorption. Significant differences were observed between the solution and solid dose formulations with respect to peak time, 15-min plasma concentration, and 0-30 min area, indicative of faster absorption from the solution; however, total plasma areas were the same for all four formulations. Comparison of plasma cloprednol levels in this study to those of a prior intravenous-oral dose study suggests that cloprednol was completely bioavailable from all formulations.

Administration, Oral↗