Population pharmacokinetic in ambulatory new-borns treated with long elimination half-time drugs for chronic asymptomatic infectious disease. Which blood sampling design and data collection process to adopt ?

S. Corvaisier1, B. Charpiat 1, G. Leboucher 1, M. Wallon 2, M. Al Kurdi 2, F. Peyron 2, C. Mounier3, and J.F. Chaulet 3.

1 Pharmacy department; 2 Parasitology department, Croix-Rousse hospital, Lyon, France; 3 Biochemistry laboratory, Desgenettes hospital, Lyon, France

Context: No well-controlled clinical trials have been done to assess oral therapy efficacy and safety in new-borns with congenital toxoplasmosis. Drugs, therapeutic regimen and duration have never been clearly defined. In our hospital, new-borns (body weight above 5 kg) receive every 10 days during 12 or 15 months a pyrimethamine – sulfadoxine combination (PYR: 1.25 mg/kg; SULF: 25 mg/kg) only labelled for single dose treatment of non severe malaria in adults. Limited PK information is available in Asian or African adults (rarely in infants): long elimination half-life (PYR: 3.4 to 5.8 days, SULF: 6.8 to 8.5 days) and wide inter-individual variability for all PK parameters. Moreover, combination’s pharmacokinetic is unknown in new-borns. In order to discuss with PAGE’s participants, the aim of this work is to present selected data collection process, and blood sampling design to perform a population pharmacokinetic study in ambulatory new-borns with asymptomatic infectious disease.

Data collection: Drugs are given to parents during pharmacy visit. They are asked to report days and hours of administrations on a calendar. Medication compliance and data collection quality are uncertain.

Blood sampling design: It takes into account the ethical issue of blood sampling in asymptomatic new-borns, their home location (300 kms around hospital), and the obvious uselessness of repeated blood sampling during visit due to the long elimination half-life. In this context, no additional blood sample for drug level measurement has been added to those needed to monitor hematological tolerance during visit in Parasitology department (see figure). 4 samples per new-born are available: at least one in absorption phase, the others are obtained in elimination phase (respectively, 2 to 5 hours, and 4 to 9 days after administration). Analysis: Data collected will be used to estimate 2 (Kel, h-1 and Vs l/kg with fixed Ka, h-1) or 3 (Ka, Kel, and Vs) PK parameters.

Reference: PAGE 8 (1999) Abstr 143 [www.page-meeting.org/?abstract=143]

Poster: poster