Pharmacokinetics of diltiazem and propranolol when administered alone and in combination

✍ Scribed by Dan C. Dimmitt; Dale K. Yu; Alfred T. Elvin; Dennis H. Giesing; Robert C. Lanman

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 428 KB
• Volume: 12
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510120705

✦ Synopsis

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-' 3 h following the final dose with an elimination half-life of 6.1 h. DTZ oral clearance was 65.1 1 h-I. PPL did not affect DTZ oral clearance and half-life during the combination treatment.

However, DTZ t,, was extended from 2-9 h to 3.5 h (p < 0.05) and C,,, was 144-7 ng ml-I. Unlike the parent drug DTZ, desacetyldiltiazem (DAD) plasma profile was elevated during the combination treatment. DAD C,,, 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 I h-' to 61.0 1 h-' while the half-life increased from 5.9 h to 8.0 h (p < 0.05). PPL C,, increased from 155.1 ng ml-' to 167.5 ngml-'