nalbuphine and Body-Weight

Nalbuphine is an opioid analgesic agent widely used for control of mild-to-severe pain. However, limited data are available on the pharmacokinetics of this drug in children. The aim of this study was to characterize the population pharmacokinetics of nalbuphine in patients with ages ranging from 1 to 11 yr and to identify patient characteristics partially explaining inter-individual variability in nalbuphine pharmacokinetic parameters.. Twenty-two children were included in this study. They received nalbuphine after surgery by continuous infusion (loading dose, 0.2 mg kg(-1) over 10 min followed by continuous infusion of 0.8 mg kg(-1) over 24 h). If pain relief was not adequate, 0.1 mg kg(-1) bolus doses were allowed in 10 min. Eleven blood samples were collected per patient. The data were analysed by non-linear mixed-effect modelling with the use of a two-compartment structural model.. Twenty patients completed the study. In the final model, the parameter values were standardized for a body weight of 70 kg using an allometric model. Population parameter estimates were: clearance 130 litre h(-1) 70 kg(-1), inter-compartment clearance 75.6 litre h(-1) 70 kg(-1), central volume of distribution 210 litre 70 kg(-1), and peripheral volume of distribution 151 litre 70 kg(-1). In the children of this study, total clearance expressed in litre h(-1) kg(-1) decreased significantly with increasing age and the elimination half-life significantly increased.. The allometric power model developed in this study best reflected the data and may be useful for dose adjustment.

Topics: Aging; Analgesics, Opioid; Body Weight; Child; Child, Preschool; Drug Administration Schedule; Female; Fundoplication; Gastroesophageal Reflux; Humans; Infant; Laparoscopy; Male; Models, Biological; Nalbuphine; Pain, Postoperative; Postoperative Care

Sucrose affects a variety of opioid-related behaviors. We hypothesized that, if sucrose ingestion alters opioidergic circuitry, opioid-induced discriminative stimulus effects would be enhanced following sucrose intake. In the present study, rats were trained to discriminate nalbuphine (3.2 mg/kg, s.c.) from saline in an operant choice procedure. After acquiring the discrimination, subjects were injected with a single nalbuphine dose (0.1-3.2 mg/kg) and given 30-min access to 30% sucrose or water. Sucrose consumption did not alter nalbuphine's discriminative stimulus effects under these conditions. During subsequent tests, training was suspended, and rats received continuous access to sucrose (9 days) or water (8 days). Chronic sucrose consumption increased the potency of nalbuphine to produce its discriminative stimulus effects by 3-fold. These findings suggest chronic sucrose consumption results in changes in opioid-system function that modulates the effects of exogenously administered opioids.

Topics: Animals; Body Weight; Conditioning, Operant; Dietary Sucrose; Discrimination Learning; Drinking; Nalbuphine; Narcotics; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Taste