title: A limited sampling strategy for the estimation of Neoral AUCs in pediatric patients.
abstract: The improved pharmacokinetics of Neoral allows the development of an accurate estimate of the full area under the concentration time curve (AUC) from a limited sampling strategy. As no such strategy has been derived from pharmacokinetic data obtained from children on 12-hourly dosing, and as patient convenience demands shorter sampling times, we derived a limited sampling strategy from 45 AUCs obtained from 19 pediatric renal transplant patients by stepwise forward multiple regression, and prospectively tested them on a separate group of 49 AUCs obtained from 18 pediatric renal transplant patients. Full cyclosporine (CsA) AUCs were obtained from samples drawn pre dose (C0) and at 2, 4, 6, 8 and 12 h post dose (C2, C4, C6, C8, and C12). High-precision predictions of full AUC were obtained based on the formula: AUC = 444 + 3.69 x C0 + 1.77 x C2 + 4. 1 x C4 (mean prediction error +/- SD = 0.3 +/- 6.4%, 95% confidence interval=-1.7% to 1.9%.) In conclusion, CsA exposure in pediatric renal transplant patients on 12-hourly Neoral dosing can be reliably predicted by an early time point-based limited sampling strategy in children. This formula has the advantage of obtaining trough as well as AUC from one brief, convenient sampling period.
authors.affiliation: Division of Nephrology and Hypertension, University of Texas-Houston, Medical School, Houston, Texas 77030, USA.
authors.forename: H U
authors.initials: HU
authors.lastname: Meier-Kriesche
authors.forename: M A
authors.initials: MA
authors.lastname: Bonilla-Felix
authors.forename: M E
authors.initials: ME
authors.lastname: Ferris
authors.forename: R
authors.initials: R
authors.lastname: Swinford
authors.forename: B D
authors.initials: BD
authors.lastname: Kahan
authors.forename: P
authors.initials: P
authors.lastname: Brannan
authors.forename: R J
authors.initials: RJ
authors.lastname: Portman
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine