title: Pharmacokinetics of ropivacaine following caudal analgesia in children.
abstract: Ropivacaine has a favourable toxicity profile for epidural anaesthesia in adults, so it may also be an appropriate agent for epidural analgesia in children. We therefore designed this study to determine the pharmacokinetic variables of ropivacaine relevant to the risk of toxicity, after caudal administration in children. We studied nine healthy children, aged 1-6 years who received 1 ml.kg-1 of ropivacaine 0.25% for caudal analgesia. Venous blood samples were collected at intervals for 12 h after injection. Total plasma concentration of ropivacaine was assayed by high performance liquid chromatography, and pharmacokinetic descriptors were estimated from the plasma concentration-time data. The median peak venous plasma concentration was 799 microg.l-1 [interquartile range (IQR) 707-1044 microg.l-1], and was reached at a median time of 1.5 h (IQR 0.5-2 h). The mean elimination half-life was 3.9 h (95% CI 2.7-5.0 h), and the mean apparent clearance and volume of distribution were 7.6+/-1. 6 ml.min-1.kg-1 (95% CI 6.1-9.1 ml.min-1.kg-1) and 2.4+/-0.6 l.kg-1 (95% CI 1.9-3.0 l.kg-1), respectively. Analgesia was satisfactory in all cases and no systemic ropivacaine toxicity was observed. Caudal administration of weight-adjusted doses of ropivacaine to children resulted in systemic exposure similar to that reported for adults. No systemic toxicity was observed. The findings strengthen predictions that the relative systemic safety of epidural ropivacaine in adults will apply to children. However, the pharmacokinetics and safety of epidural ropivacaine need to be studied further in children with circumstances that affect drug disposition and systemic tolerance.
authors.affiliation: Department of Anaesthesia, Princess Margaret Hospital for Children, Perth, Western Australia.
authors.forename: W
authors.initials: W
authors.lastname: Habre
authors.forename: R
authors.initials: R
authors.lastname: Bergesio
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.forename: P
authors.initials: P
authors.lastname: Hackett
authors.forename: D
authors.initials: D
authors.lastname: Joyce
authors.forename: C
authors.initials: C
authors.lastname: Sims
mesh_terms: D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015360:Analgesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D016001:Confidence Intervals; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D007223:Infant; D008657:Metabolic Clearance Rate; D000077212:Ropivacaine; D012449:Safety; D014018:Tissue Distribution
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine