Pharmacokinetics in Stable Pediatric Patients Switching from Liquid LPV/r to the Pediatric 100/25-mg Tablets: The Tiny Tabs Study
Janice Piatt*1, L Clarke-Steffen1, J Foti2, C Fletcher3, and B Robbins3
1Phoenix Children`s Hosp, AZ, US; 2Seattle Children`s Hosp, WA, US; and 3Univ of Nebraska Med Ctr, Omaha, US
Background: Lopinavir/ritonavir (LPV/r) is a protease inhibitor recommended for the treatment of HIV+ pediatric patients. The liquid formulation is frequently disliked due to its foul taste. The development of the pediatric tablet (100/25 mg) that can be given to younger patients allows the switch from the unpalatable liquid to a tablet. This study was designed to evaluate the comparability, efficacy, and tolerability in stable patients switching to the 100/25-mg tablet from the oral solution.
Methods: Pediatric patients 3 to 18 years of age with stable viral loads <1000 copies for >6 months on HAART therapy with liquid LPV/r and weighing <15 kg were offered enrollment in the study. All dosing was based on the manufacturer’s prescribing information. Intensive pharmacokinetic sampling was performed on children taking the liquid formulation prior to the switch to the tablet form. Pharmacokinetic samples were drawn at trough, 2, 4, 6, and 8 hours after LPV/r dosing and repeated at 1 month post switch. Random pharmacokinetic levels were obtained at 12 and 24 weeks post switch. LPV and r concentrations were determined by UPLC. Pharmacokinetic parameters were determined by noncompartmental methods. Chemistry readings, CD4, viral load, and lipid levels were obtained at baseline and at the follow-up visits. A patient satisfaction questionnaire was completed pre-switch and at all post-switch follow-up visits.
Results: We enrolled 8 subjects who completed the study; mean age was 7 years (range 4.5 to 9). The sample was 50% Hispanic and 50% African American, 62.5% females. Backbone regimens included 2 drugs from among nevirapine, lamivudine, stavudine, abacavir, and didanosine. Pharmacokinetic analysis showed mean LPV AUC and Cmax ratios between liquid and tablet formulations to be 1.01 and 1.02, indicating that overall, the concentrations achieved with the different formulations were essentially the same. All pre-dose (trough) concentrations were >1000 ng/mL. No adverse events or treatment discontinuation occurred during the study. CD4 and viral loads remained stable after the switch with no treatment failures in patients switching from the oral solution to the 100/25-mg tablet.
Conclusions: Pharmacokinetics show therapeutic ranges for all children in the study. Switching from the oral LPV/r solution to the pediatric 100/25-mg tablet provides similar pharmacodynamics for patients.