Summary
On the basis of reports that diltiazem binds to the hepatic microsomal enzymes and inhibits the metabolism of coadministered drugs, we investigated the effect of a 240 mg daily dose of the calcium channel blocker for a week on theophylline metabolism in 8 healthy male volunteers aged 20–24 years and weighing 56–68 kg.
None of theophylline half-life (9.7 h), volume of distribution (0.514 l·kg−1) and total clearance (0.63 ml·min−1·kg−1) after pretreatment differed from the respective control value of 9.5 h, 0.519 l·kg−1 and 0.65 ml·min−1·kg−1.
In 6 of the volunteers, 600-mg daily dose of rifampicin for a week induced theophylline metabolism. The control half-life of the bronchodilator (9.6 h) was reduced to 5.5 h and its total clearance (0.64 ml·min−1·kg−1) increased to 1.22 ml·min−1·kg−1. There was no change in volume of distribution.
In these 6 volunteers, intake of diltiazem (240 mg daily), concurrently with rifampicin for a week, significantly elevated theophylline half-life to 6.2 h as well as reduced its clearance to 1.03 ml·min−1·kg−1. The volume of distribution did not change. Furthermore, diltiazem-induced absolute fall in theophylline clearance correlated significantly with its post-rifampicin value (r=0.895).
It is suggested that diltiazem has no effect on theophylline metabolism in non-induced subjects. However, rifampicin-induced metabolism of the bronchodilator could be attenuated by diltiazem when the two drugs are given concurrently.
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Adebayo, G.I., Akintonwa, A. & Mabadeje, A.F.B. Attenuation of rifampicin-induced theophylline metabolism by diltiazem/rifampicin coadministration in healthy volunteers. Eur J Clin Pharmacol 37, 127–131 (1989). https://doi.org/10.1007/BF00558219
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DOI: https://doi.org/10.1007/BF00558219