Drugs online research references
Arch Toxicol Suppl. 1984;7:256-9.
The influence of two histamine H2-receptor antagonists, cimetidine and ranitidine, on the plasma levels and clinical effect of nifedipine and metoprolol.
Kirch W, Ramsch K, Janisch HD, Ohnhaus EE.
In six healthy volunteers pharmacokinetic and pharmacodynamic interaction of metoprolol and nifedipine with cimetidine and ranitidine was investigated after 1 week of monotherapy with nifedipine and metoprolol and after 1 week each of combined treatment of these drugs with the H2-receptor antagonists. Ranitidine led to a 50% increase in mean peak plasma levels and in the area under the plasma level time curve (AUC) of metoprolol (p less than 0.05) and to an insignificant 30% rise in these parameters of nifedipine (p less than 0.05). Cimetidine increased metoprolol's peak plasma levels of AUC by about 60% (p less than 0.05) and those of nifedipine by 80% (p less than 0.05). Compared to monotherapy with metoprolol beta blocking activity measured by exercise induced tachycardia was not significantly stronger inhibited under the combined treatment of metoprolol with each of the two H2-receptor antagonists. On the other hand the antihypertensive effect of nifedipine was significantly increased during concurrent administration of cimetidine in seven hypertensive patients when compared with monotherapy.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6151387&dopt=Abstract
Pharmacogenetics. 2000 Jul;10(5):425-38.
Effect of gender, sex hormones, time variables and physiological urinary pH on apparent CYP2D6 activity as assessed by metabolic ratios of marker substrates.
Labbe L, Sirois C, Pilote S, Arseneault M, Robitaille NM, Turgeon J, Hamelin BA.
Faculty of Pharmacy, Laval University, Ste-Foy, Quebec, Canada.
The effects of gender, time variables, menstrual cycle phases, plasma sex hormone concentrations and physiologic urinary pH on CYP2D6 phenotyping were studied using two widely employed CYP2D6 probe drugs, namely dextromethorphan and metoprolol. Phenotyping on a single occasion of 150 young, healthy, drug-free women and men revealed that the dextromethorphan: dextrorphan metabolic ratio (MR) was significantly lower (P < 0.0001) in 56 female extensive metabolizers (0.008+/-0.021) compared to 86 male extensive metabolizers (0.020 +/-0.040). Urinary pH was a significant predictor of dextromethorphan: dextrorphan MRs in men and women (P < 0.001). Once-a-month phenotyping with dextromethorphan of 12 healthy young men (eight extensive metabolizers and four poor metabolizers) over a 1-year period, as well as every-other-day phenotyping with dextromethorphan of healthy, pre-menopausal women (10 extensive metabolizers and 2 poor metabolizers) during a complete menstrual cycle, did not follow a particular pattern and showed similar intrasubject variability ranging from 24.1% to 74.5% (mean 50.9%) in men and from 20.5% to 96.2% (mean 52.0%) in women, independent of the CYP2D6 phenotype (P = 0.342). Using metoprolol as a probe drug, considerable intrasubject variability (38.6+/- 12.0%) but no correlation between metoprolol: alpha-hydroxymetoprolol MRs and pre-ovulatory, ovulatory and luteal phases (mean +/- SD metoprolol: a-hydroxymetoprolol MRs: 1.086+/- 1.137 pre-ovulatory; 1.159+/-1.158 ovulatory and 1.002+/-1.405 luteal phase; P> 0.9) or 17beta-oestradiol, progesterone or testosterone plasma concentrations was observed. There was a significant inverse relationship between physiologic urinary pH and sequential dextromethorphan: dextrorphan MRs as well as metoprolol: alpha-hydroxymetoprolol MRs in men and women, with metabolic ratios varying up to six-fold with metoprolol and up to 20-fold with dextromethorphan (ANCOVA P < 0.001). We conclude that apparent CYP2D6 activity is highly variable, independent of menstrual cycle phases, sex hormones, time variables or phenotype. Up to 80% of the observed variability can be explained by variations of urinary pH within the physiological range. An apparent phenotype shift as a result of variations in urinary pH may be observed in individuals who have metabolic ratios close to the population antimode.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10898112&dopt=Abstract
Biochem Pharmacol. 1990 Oct 15;40(8):1769-71.
Acute effect of thyroid hormone on insulin secretion in rats.
Ikeda T, Fujiyama K, Hoshino T, Tanaka Y, Takeuchi T, Mashiba H, Tominaga M.
First Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
To elucidate the mechanism of thyroid hormone-induced hyperinsulinemia, the acute and direct effect of thyroid hormone administration on insulin secretion was investigated in rats in vivo and in vitro. In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion. The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL, while blood glucose and plasma glucagon were unchanged. This phenomenon was inhibited completely by the preadministration of oxprenolol hydrochloride (2 mg/kg, s.c.), and inhibited partly by the preadministration of metoprolol tartrate (35 mg/kg, s.c.). These results suggest that thyroid hormone induces hyperinsulinemia via beta-adrenergic stimulation in the rat.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2242013&dopt=Abstract
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