EFFECT OF NIFEDIPINE ON ANTIPYRINE AND THEOPHYLLINE DISPOSITION

On the basis of reports that some calcium channel blockers impair the elimination of some drugs, the effect of nifedipine on the disposition of antipyrine and theophylline was assessed in healthy volunteers. Antipyrine half‐life of 10·04 ± 1·43 h (mean ± SD) after a week intake of nifedipine (20 mg twice daily) was not significantly different from the control value of 10·64 ± 2·15 h; nor was that of 10·02 ± 1·49 h after 2 weeks pretreatment with the calcium channel blocker in eight healthy volunteers. Control antipyrine clearance (ml min−1) of 44·40 ± 10·58 was not significantly different from that of 45·66 ± 9·34 and 46·87 ± 9·63 after nifedipine pretreatment of 1 and 2 weeks, respectively. Similarly volume of distribution was unaltered: 0·601 ± 0·074. 0·591 ± 0·078 and 0·602 ± 0·051 1 kg−1, respectively. A week pretreatment with nifedipine did not significantly alter either of theophylline half‐life (7·32 ± 0·81 h (control) to 7·50 ± 0·80 h) or clearance (42·10 ± 5·84 ml min−1 (control) to 43·77 ± 4·00 ml min−1) in six volunteers. However the change in volume of distribution: 0·451 ± 0·053 1kg−1 (control) to 0·483 ± 0·0621 kg−1 was significant (p < 0·025). Generally, theophylline plasma levels were lower after nifedipine pretreatment and the difference was significant at 2 and 4 h post‐dosing (p < 0·05). It is suggested that nifedipine, unlike diltiazem and verapamil, is unlikely to interfere with the functional integrity of the hepatic mixed‐function oxygenase enzymes, but might displace theophylline from plasma protein. Copyright © 1990 John Wiley & Sons, Ltd.