Pharmacokinetics of nalbuphine in infants, young healthy volunteers, and elderly patients.
Nalbuphine is a new agonist and antagonist opioid analgesic agent that undergoes an important hepatic metabolism. In this study, we compared the pharmacokinetics of intravenous and oral nalbuphine in three groups of subjects: group I consisted of 14 children from 1 1/2 to 5 years of age (group IA) and from 5 through 8 1/2 years of age (group IB), group II consisted of 9 healthy male volunteers from 23 to 32 years of age, and group III consisted of 9 elderly patients from 65 to 90 years of age. All subjects and patients had normal hepatic and renal functions. The children received an intravenous injection of nalbuphine (0.2 mg/kg), and the subjects and patients in groups II and III received, at random, 10 mg intravenous injections and 30 mg oral doses of nalbuphine on two separate occasions. The distribution of nalbuphine was not modified with age. Elimination half-life (t1/2) was significantly shorter in group I (0.9 hour) than it was in group II (1.9 hours) and in group III (2.3 hours). Systemic clearance of nalbuphine decreased significantly with age. Absolute bioavailability of nalbuphine increased from F = 12% in group II to 46.3% in group III (p less than 0.01). These findings suggest that doses and rates of administration of nalbuphine should be adapted in younger patients and in elderly patients.
Jaillon
P
P
Département de Pharmacologie Clinique, CHU Saint-Antoine, Paris, France.
Gardin
M E
ME
Lecocq
B
B
Richard
M O
MO
Meignan
S
S
Blondel
Y
Y
Grippat
J C
JC
Bergnieres
J
J
Vergnoux
O
O
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009019:Morphinans / Q000493:pharmacokinetics*; D009266:Nalbuphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D009019:Morphinans; D009266:Nalbuphine