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Pharmacokinetics of diltiazem and propranolol when administered alone and in combination

Multiple oral doses of diltiazem (DTZ) and propranolol (PPL, 60 mg every 8 h daily for 13 doses) were administered to 14 healthy volunteers alone and in combination on three separate occasions. Serial blood samples were collected up to 24 h after dose 13 on day 5 to determine possible pharmacokinetic interactions between the two drugs. When administered alone, DTZ concentration peaked at 161·4 ng ml−1 3 h following the final dose with an elimination half‐life of 6·1 h. DTZ oral clearance was 65·11 h−1. PPL did not affect DTZ oral clearance and half‐life during the combination treatment. However, DTZ tmax was extended from 2·9 h to 3·5 h (p < 0·05) and Cmax was 144·7 ng ml−1. Unlike the parent drug DTZ, desacetyldiltiazem (DAD) plasma profile was elevated during the combination treatment. DAD Cmax and AUC both increased approximately 20 per cent (p < 0·05). PPL pharmacokinetics were altered as well. Oral clearance of PPL decreased from 80·4 1 h−1 to 61·0 1 h−1 while the half‐life increased from 5·9 h to 8·0 h (p < 0·05). PPL Cmax increased from 155·1 ng ml−1 to 167·5 ng ml−1.