Effects of Diltiazem and Cimetidine on Theophylline Oxidative Metabolism

Ohashi, Kyoichi; Sakamoto, Kouichi; Sudo, Toshiaki; Tateishi, Tomonori; Fujimura, Akio; Shiga, Tsuyoshi; Ebihara, Akio

doi:10.1002/j.1552-4604.1993.tb03925.x

Cited by 6 publications

(2 citation statements)

References 23 publications

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“…28 (4) 1995 The situation is similarly disparate for the group of calcium antagonists (calcium channel blockers). Christopher et aU 223 ] and Smith et aU226] did not find an interaction between diltiazem and theophylline, but other investigators determined a reduction in clearance (9 to 22% )J224, 238,243] Nifedipine appears to the calcium channel blocker that possess the least influence on theophylline parameters. Robson and colleagues [230] observed a moderate decrease in theophylline clearance by 9%.…”

Section: Enzyme Inhibitionmentioning

confidence: 93%

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Tröger

Meyer

1995

Clinical Pharmacokinetics

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Theophylline has been widely used as a bronchodilatory drug for the treatment of neonatal apnoea in premature newborns and patients with obstructive airways disease. The development of analytical equipment and procedures to determine the systemic concentration of theophylline renders it possible to improve the effectiveness of theophylline therapy and reduce the incidence of toxic and adverse effects. Since the beginning of the 1970s, endogenous and exogenous factors (e.g. age, blood pH, concomitant diseases and drug therapy, meal preparation procedure, nutritional habits, pregnancy, gender, smoking and, to a lesser extent, biorhythms), influencing nearly all parameters of theophylline pharmacokinetics have been described. Drug absorption depends on galenic formulation, drug delivery, nutritional habits and the chemical derivatives used. The mean plasma protein binding rates depend on the method of plasma protein determination: acidic blood pH values and advanced age may result in reduced plasma proteins. The volume of distribution depends primarily on age; it is 2-fold greater in newborns than in adults. Furthermore, changes in blood pH values, the plasma protein content and the administration of concomitant drugs may vary this parameter. Biotransformation is the most clinically important pharmacokinetic parameter. Hepatic metabolism accounts for 90% of the metabolism of theophylline. Essentially, 2 microsomal isoenzymes of the cytochrome P450 system appear to be responsible for the N-methylation and 8-hydroxylation of the drug. Age and concomitant disease are the major endogenous effectors influencing biotransformation of theophylline, whereas biorhythms, gender and pregnancy are of lesser importance. Exogenous factors, such as concomitantly administered drugs, smoking and nutritional factors, affect biotransformation by inducing or inhibiting the metabolising enzymes. Because of intra- and interindividual variability in the pharmacokinetics of theophylline, which may be increased by the presence of endogenous and/or exogenous effectors, it is necessary to supervise theophylline therapy by therapeutic drug monitoring if target concentrations are to be achieved.

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Section: Enzyme Inhibitionmentioning

confidence: 93%

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Tröger

Meyer

1995

Clinical Pharmacokinetics

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“…Nevertheless, the oral clearance of several CYP3A substrates, including cyclosporine (112), midazolam (131), triazolam (132), morizicine (133), and quinidine (134) were found to be markedly (>75%) reduced when diltiazem was co-administered compared to the drug substrate alone. Additionally, diltiazem inhibited the CYP3A-mediated metabolism, of carbamazepine (135) and theophylline (136), which have low intrinsic clearances that preclude the likelihood of the discrepancy resulting from selective intestinal CYP3A inhibition. Also, a single diltiazem dose has been found to reduce the systemic clearance of both midazolam and alfentanil (137).…”

Section: In Vitro-in Vivo Predictions Of Cyp3a Inhibitionmentioning

confidence: 98%

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

Thummel

Wilkinson

1998

Annu. Rev. Pharmacol. Toxicol.

762

515

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Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its localization in high amounts both in the small intestinal epithelium and liver makes it a major contributor to presystemic elimination following oral drug administration. Drug interactions involving enzyme inhibition or induction are common following the coadministration of two or more CYP3A substrates. Studies using in vitro preparations are useful in identifying such potential interactions and possibly permitting extrapolation of in vitro findings to the likely in vivo situation. Even if accurate quantitative predictions cannot be made, several classes of drugs can be expected to result in a drug interaction based on clinical experience. In many instances, the extent of such drug interactions is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs.

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Cytochrome P450 and Its Role in Veterinary Drug Interactions

Trepanier

2006

Veterinary Clinics of North America: Small Animal Practice

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Effects of Diltiazem and Cimetidine on Theophylline Oxidative Metabolism

Cited by 6 publications

References 23 publications

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

Cytochrome P450 and Its Role in Veterinary Drug Interactions

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