Selectivity and Dose-dependency of the Inhibitory Effect of Propranolol on Theophylline Metabolism in Man

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 1985 Sep 1

PMID 4041342

Citations 11

Authors

J O Miners

L M Wing

K J Lillywhite

R A Robson

Affiliations

Soon will be listed here.

Abstract

The effects of separate 5 day pretreatments of propranolol 120 mg day-1 and 720 mg day-1 on theophylline clearance and metabolism at steady-state were determined in seven healthy males. Propranolol 120 mg day-1 decreased theophylline plasma clearance (CL) by 30%. Clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylated products by 42-43% and clearance to the 8-hydroxylation product by 27%. Propranolol 720 mg day-1 decreased theophylline CL by 52%. Again, clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylation products by 73-77% and clearance to the 8-hydroxylation product by 44%. These data are consistent with a dose-dependent and selective inhibitory effect of propranolol on the separate forms of cytochrome P-450 involved in theophylline demethylation and 8-hydroxylation.

Citing Articles

Effects of Lasmiditan on Cardiovascular Parameters and Pharmacokinetics in Healthy Subjects Receiving Oral Doses of Propranolol.

Tsai M, Case M, Ardayfio P, Hochstetler H, Wilbraham D Clin Pharmacol Drug Dev. 2020; 9(5):629-638.

PMID: 31950732 PMC: 7384162. DOI: 10.1002/cpdd.768.

Perpetrators of pharmacokinetic drug-drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment.

Polasek T, Lin F, Miners J, Doogue M Br J Clin Pharmacol. 2011; 71(5):727-36.

PMID: 21223357 PMC: 3093078. DOI: 10.1111/j.1365-2125.2011.03903.x.

Influence of endogenous and exogenous effectors on the pharmacokinetics of theophylline. Focus on biotransformation.

Troger U, Meyer F Clin Pharmacokinet. 1995; 28(4):287-314.

PMID: 7648758 DOI: 10.2165/00003088-199528040-00003.

Metabolism of theophylline by cDNA-expressed human cytochromes P-450.

Ha H, Chen J, Freiburghaus A, Follath F Br J Clin Pharmacol. 1995; 39(3):321-6.

PMID: 7619675 PMC: 1365010. DOI: 10.1111/j.1365-2125.1995.tb04455.x.

Characterisation of theophylline metabolism in human liver microsomes.

Robson R, Matthews A, Miners J, McManus M, Meyer U, Hall P Br J Clin Pharmacol. 1987; 24(3):293-300.

PMID: 3663445 PMC: 1386249. DOI: 10.1111/j.1365-2125.1987.tb03172.x.

References

Greenblatt D, Franke K, Huffman D . Impairment of antipyrine clearance in humans by propranolol. Circulation. 1978; 57(6):1161-64. DOI: 10.1161/01.cir.57.6.1161. View

Ochs H, Greenblatt D, Woo E, Franke K, Smith T . Effect of propranolol on pharmacokinetics and acute electrocardiographic changes following intravenous quinidine in humans. Pharmacology. 1978; 17(6):301-6. DOI: 10.1159/000136870. View

Routledge P, SHAND D . Clinical pharmacokinetics of propranolol. Clin Pharmacokinet. 1979; 4(2):73-90. DOI: 10.2165/00003088-197904020-00001. View

PRITCHARD J, Schneck D, HAYES Jr A . The inhibition of rat hepatic microsomal propranolol metabolism by a covalently bound reactive metabolite. Res Commun Chem Pathol Pharmacol. 1980; 27(2):211-22. View

Ochs H, Carstens G, Greenblatt D . Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. N Engl J Med. 1980; 303(7):373-7. DOI: 10.1056/NEJM198008143030705. View

Conrad K, Nyman D . Effects of metoprolol and propranolol on theophylline elimination. Clin Pharmacol Ther. 1980; 28(4):463-7. DOI: 10.1038/clpt.1980.189. View

Foenander T, Birkett D, Miners J, Wing L . The simultaneous determination of theophylline, theobromine and caffeine in plasma by high performance liquid chromatography. Clin Biochem. 1980; 13(3):132-4. DOI: 10.1016/s0009-9120(80)90819-x. View

Peet M, Middlemiss D, YATES R . Pharmacokinetic interaction between propranolol and chlorpromazine in schizophrenic patients. Lancet. 1980; 2(8201):978. DOI: 10.1016/s0140-6736(80)92135-2. View

Grygiel J, Birkett D . Cigarette smoking and theophylline clearance and metabolism. Clin Pharmacol Ther. 1981; 30(4):491-6. DOI: 10.1038/clpt.1981.193. View

10.

Bax N, Lennard M, Tucker G . Inhibition of antipyrine metabolism by beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1981; 12(6):779-84. PMC: 1401937. DOI: 10.1111/j.1365-2125.1981.tb01306.x. View

11.

Conrad K, Byers 3rd J, FINLEY P, Burnham L . Lidocaine elimination: effects of metoprolol and of propranolol. Clin Pharmacol Ther. 1983; 33(2):133-8. DOI: 10.1038/clpt.1983.20. View

12.

Birkett D, Miners J, Attwood J . Secondary metabolism of theophylline biotransformation products in man--route of formation of 1-methyluric acid. Br J Clin Pharmacol. 1983; 15(1):117-9. PMC: 1427820. DOI: 10.1111/j.1365-2125.1983.tb01475.x. View

13.

Grygiel J, Miners J, Drew R, Birkett D . Differential effects of cimetidine on theophylline metabolic pathways. Eur J Clin Pharmacol. 1984; 26(3):335-40. DOI: 10.1007/BF00548764. View

14.

Tucker G, Bax N, Lennard M, Bharaj H, Woods H . Effects of beta-adrenoceptor antagonists on the pharmacokinetics of lignocaine. Br J Clin Pharmacol. 1984; 17 Suppl 1:21S-28S. PMC: 1463282. DOI: 10.1111/j.1365-2125.1984.tb02424.x. View

15.

Hawksworth G, Betts T, Crowe A, Knight R, Parry K, Petrie J . Diazepam/beta-adrenoceptor antagonist interactions. Br J Clin Pharmacol. 1984; 17 Suppl 1:69S-76S. PMC: 1463275. DOI: 10.1111/j.1365-2125.1984.tb02431.x. View

16.

Ochs H, Greenblatt D . Propranolol interactions with diazepam, lorazepam, and alprazolam. Clin Pharmacol Ther. 1984; 36(4):451-5. DOI: 10.1038/clpt.1984.203. View

17.

Miners J, Wing L, Lillywhite K, Smith K . Failure of 'therapeutic' doses of beta-adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine. Br J Clin Pharmacol. 1984; 18(6):853-60. PMC: 1463673. DOI: 10.1111/j.1365-2125.1984.tb02555.x. View