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Biomedical subjects

D J Back

Publications and source records attributed to D J Back.

At least 217 records · Page 12Linked to original sources
PubMed1980

Phenobarbitone interaction with oral contraceptive steroids in the rabbit and rat.

1 The effect of phenobarbitone on the single dose pharmacokinetics of the synthetic steroids, ethinyloestradiol (EE2) and norethisterone, has been studied in the rabbit and rat. 2 EE2 is subject to an extensive first pass effect (96%). The plasma clearance of EE2 approaches total hepatic blood flow. It is suggested that a secondary peak in EE2 plasma concentration time curves at 5 h is due to enterohepatic recycling. Phenobarbitone had no effect on plasma EE2 concentrations following intravenous administration and produced a variable decrease after oral administration. 3 In phenobarbitone-treated rabbits, following intravenous administration of norethisterone there was no significant change in the area under the curve (AUC) compared to controls. In contrast, following oral administration of norethisterone to treated rabbits, the AUC was 20% and the peak plasma concentration 17% of that in controls. 4 The data in rabbits are consistent with drugs which are highly extracted by the liver. 5 In rats, phenobarbitone had no effect on plasma norethisterone concentrations following intravenous or hepatic portal (bolus) administration, but caused a decrease in systemic availability after both infusion into the portal vein (over a period of 5 min) and oral administration. 6 It is concluded that the rate of delivery of norethisterone to the liver is important in determining whether or not enzyme induction will cause an increased first pass effect. 7 Phenobarbitone caused an increase in conjugation of norethisterone in the gastrointestinal tract of rats.

Animals↗
PubMed1979

The effect of rifampicin on norethisterone pharmacokinetics.

The pharmacokinetics of norethisterone have been studied in 8 women during and one month after treatment with rifampicin (450--600 mg/day). Rifampicin caused a significant reduction in the A.U.C. of a single dose of 1 mg norethisterone from 37.8 +/- 13.1 to 21.9 +/- 5.9 ng/ml X h (p less than 0.01). The plasma norethisterone half life (beta-phase) was also reduced from 6.2 +/- 1.7 to 3.2 +/- 1.0 h (p less than 0.0025). In one additional woman on long term oral contraceptive therapy the 12 hour plasma norethisterone concentration was reduced by rifampicin from 12.3 ng/ml to 2.3 ng/ml. Rifampicin caused a significant increase in antipyrine clearance, 6 beta-hydroxycortisol excretion and plasma gamma-glutamyltranspeptidase activity but there was no significant correlations between changes in these indices of liver microsomal enzyme induction. There was a significant correlation between the percentage increase in antipyrine clearance and the percentage decrease in norethisterone A.U.C. during rifampicin. The changes in norethisterone pharmacokinetics during rifampicin therapy are compatible with the known enzyme inducing effect of rifampicin.

Adolescent↗
PubMed1979

An investigation of the pharmacokinetics of ethynylestradiol in women using radioimmunoassay.

A radioimmunoassay for ethynylestradiol (EE) which is applicable to plasma samples obtained from women, who have taken a combination type oral contraceptive, has been developed and fully validated. Plasma concentration of EE rise to a peak of 128 pg/ml following the oral administration of 50 microgram EE. Following the intravenous administration of the same dose of EE, plasma concentrations of the steroid declined biexponentially, the two half-lives being 0.83 and 6.75 hours. Comparison of the results of the intravenous and oral administration of the steroid suggested that its oral bioavailability is 42%. Although EE thus has a lower bioavailability than norethindrone, the pharmacokinetics of the two steroids, as reflected by half-lives, plasma clearance and volume of distribution, are very similar. The occurrence of a secondary peak in plasma at around 12 hours after dosing gave strong evidence that EE undergoes enterohepatic circulation in women; an event that may have considerable clinical significance.

Administration, Oral↗
PubMed1978

The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow in the rat.

The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow was investigated in the rat. Liver blood flow with pentobarbital anaesthesia was 40% greater than with urethane. Hepatic portal vein catheterization had no effect under pentobarbital anaesthesia whereas it produced an 18% fall in liver blood flow with urethane.

Animals↗