M. du Preez1, J. Botha1, and L. McFadyen2
Departments of Pharmacology, University of Natal1, and University of Durban-Westville2, Durban, South Africa
The aim of the study was to determine the relationship between theophylline concentration and its effect in reducing incidences of neonatal apnoea.
Forty-four premature neonates with average (SD) birth weight 1.26 (0.25) kg, and gestational age 30.6 (1.4) weeks, were entered into the study. For this study apnoea was defined as cessation of breathing for five seconds or longer, and was recorded by measuring nasal air flow on a neonatal capnograph. Baseline recordings were obtained before the theophylline loading dose was given (day zero). Subsequent recordings were made after the loading dose (termed day one) and then on the following two days of maintenance treatment – termed day two and three. Blood samples were taken during the monitoring periods. Serum theophylline concentrations were analysed by the Syva Emit system. The average levels were 8.0 mg/L (range 0 – 42 mg/L).
The concentration to count data was analysed using NONMEM version 4, level 2.1 double precision. The data was better described by an asymptotic count model than by a linear model, with a reduction in objective function of 100. The following equation described the asymptotic model:
Count = P1+P2[1-(conc/P3+conc)]
conc = concentration
P1 = 4.5 = residual counts not influenced by drug
P2 = 7.9 = with full drug effect
P1+P2 = typical baseline count
P3 = 3.9
conc/P3+conc = fractional reduction due to drug
The influence of the covariates day, body weight, and gestational age were investigated.
We would like to thank Prof S Beal (University of California, San Francisco) for supplying the relevant codes and Dr Raymond Miller (FDA) for assistance in getting the count model to run.
Reference: PAGE 6 () Abstr 664 [www.page-meeting.org/?abstract=664]
Poster: poster