Palatability and relative bioavailability of an extemporaneous carbamazepine oral suspension
Bloomer, D.; Dupuis, L.L.; MacGregor, D.; Soldin, S.J.
Clinical Pharmacy 6(8): 646-649
1987
ISSN/ISBN: 0278-2677 PMID: 3691011 Document Number: 298283
The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspensions was tested, and the bioavailability of the unflavored suspension relative to that of the tablet used in its manufacture was determined in a randomized, crossover study of 12 healthy volunteers. Carbamazepine 400 mg was administered with a glass of water as either 20 mL of unflavored oral suspension (20 mg/mL) or two 200-mg tablets. Subjects were randomly assigned to receive first either the tablets or the suspension in crossover fashion on two days separated by at least two weeks. Blood samples were taken just before and at various times up to 72 hours after the carbamazepine dose. Serum samples were assayed for carbamazepine content by high-performance liquid chromatography. Of five flavored and unflavored carbamazepine suspensions tested in eight volunteers, the cherrymint formulation was the least palatable. There was no trend in preference among the remaining suspensions (banana, tutti-frutti, grape, and unflavored). Mean values of maximum serum concentrations and absorption rate constant were significantly greater for the unflavored suspension (5.7 mg/L [24 .mu.mol/L] and 0.832 hr-1, respectively) than for the tablet (4.9 mg/L [20.8 .mu.mol/L] and 0.266 hr-1, respectively). The mean time to maximum concentration was significantly shorter after suspension administration (3.87 hours) than after tablet administration (11.8 hours). There was no significant difference in the extent of absorption of the tablet and suspension formulation as reflected by the corrected values of the area under the serum concentration-versus-time curves. The mean (.+-. S.D.) bioavailability of the suspension relative to the tablet was 94.46% .+-. 20.42 (range 76.35-132.72%). The order of administration (tablet versus suspension) did not influence the bioavailability of the carbamazepine suspension. Since the suspension produced significantly earlier and higher peak concentrations compared with the tablet, patients receiving the suspension may require more frequent administration of lower doses of carbamazepine to avoid toxicity.