The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine.
The disposition of oxcarbazepine was studied in 12 young and 12 elderly healthy male and 12 young and 12 elderly healthy female volunteers, with emphasis on the influence of age. Oxcarbazepine was administered as a single dose of either 300 mg (men) or 600 mg (women), followed by multiple-dose (300 mg) administration twice a day for 7 days (men) or 6 days (women). Semilogarithmic plasma concentration-time curves showed an increasing decline at decreasing concentrations. Accumulation of the pharmacologically active metabolite monohydroxycarbamazepine was found to be more than one would anticipate on the basis of linear and unchanged pharmacokinetics. Saturation did not seem to occur at the level of renal excretion. No apparent differences between male and female volunteers were observed. A significant higher maximum concentration, higher area under the curve parameters, and a lower elimination rate constant were observed in the elderly. These observations are in line with a smaller renal clearance of monohydroxycarbamazepine in the elderly group. In a clinical situation, these age-related differences are not likely to have important implications. In general, treatment with oxcarbazepine was well tolerated.
Pharma Bio-Research International B.V., Assen, The Netherlands.
P N
PN
van Heiningen
M D
MD
Eve
B
B
Oosterhuis
J H
JH
Jonkman
H
H
de Bruin
J A
JA
Hulsman
A
A
Richens
P K
PK
Jensen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D012016:Reference Values; D012727:Sex Characteristics
D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine