BIOMAT Database Logo BIOMAT Database Logo

Pharmacokinetics and hypotensive effect of diltiazem in rabbits after a single intravenous administration: effect of phenobarbital. 1998

P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics and Metabolism Laboratory, College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.

Metabolism of the widely used calcium antagonist diltiazem (DTZ) is an important contributing factor to its therapeutic effects. In order to study the effects of CYP3A induction on the pharmacokinetics and haemodynamic effect of DTZ, it was administered as a single 5 mg/kg dose i.v. to two groups of New Zealand white rabbits (n = 6 in each group). Prior to the injection, one of the groups received phenobarbital 20 mg/kg s.c. two times a day for 3 days to ensure CYP3A induction, and the other received normal saline. A third group of animals (n = 6) received neither phenobarbital nor DTZ, and served as the control. Blood samples, systolic and diastolic blood pressure (SBP and DBP), and heart rate (HR) recordings were obtained from each rabbit up to 7 h, and urine samples for 48 h post-dose. Plasma concentrations of DTZ and its metabolites were determined by HPLC. The results showed that phenobarbital increased the Cl and Vdss of DTZ from 24 +/- 14 to 51 +/- 4.9 ml/min/kg and from 1.9 +/- 1.2 to 3.8 +/- 0.7 l/kg, respectively (p < 0.05). It also decreased the plasma concentrations of DTZ and all the measured metabolites in this study. Both phenobarbital and DTZ decreased SBP and DBP significantly without affecting the HR.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D010089 Oxidoreductases, N-Demethylating N-Demethylase,N-Demethylases,Oxidoreductases, N Demethylating,Demethylating Oxidoreductases, N,N Demethylase,N Demethylases,N Demethylating Oxidoreductases,N-Demethylating Oxidoreductases
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004110 Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions. Aldizem,CRD-401,Cardil,Cardizem,Dilacor,Dilacor XR,Dilren,Diltiazem Hydrochloride,Diltiazem Malate,Dilzem,Tiazac,CRD 401,CRD401
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005260 Female Females

Related Publications

P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics and metabolism of diltiazem in rabbits after a single intravenous or single oral administration.
January 1991, European journal of drug metabolism and pharmacokinetics,
P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics of diltiazem after intravenous and oral administration.
January 1983, European journal of clinical pharmacology,
P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits.
March 2010, Interdisciplinary toxicology,
P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics of levamisole in rabbits after intravenous administration.
March 1992, Journal of veterinary pharmacology and therapeutics,
P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics of ethinyloestradiol in rabbits after intravenous administration.
May 1996, Contraception,
P K Yeung, and J D Feng, and S J Buckley
[Ethmozin pharmacokinetics after a single intravenous administration].
May 1982, Kardiologiia,
P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics of thymoxamine in rabbits after ophthalmic and intravenous administration.
January 1994, European journal of drug metabolism and pharmacokinetics,
P K Yeung, and J D Feng, and S J Buckley
Pharmacokinetics of vitacoxib in rabbits after intravenous and oral administration.
May 2019, Journal of veterinary pharmacology and therapeutics,
P K Yeung, and J D Feng, and S J Buckley
[Pharmacokinetics of breviscapine in dogs and rabbits following single intravenous administration].
October 2005, Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials,
P K Yeung, and J D Feng, and S J Buckley
Medroxyprogesterone acetate plasma pharmacokinetics after intravenous administration in rabbits.
January 1987, Cancer chemotherapy and pharmacology,
Copied contents to your clipboard!