Mean population pharmacokinetic values were similar to those obtained with NONMEM for gentamicin in other neonates of similar age. Gender was found to be a determinant of CL, with girls clearing faster than boys.

Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.

The aims of the study were to estimate the pharmacokinetic parameters, clearance rate (CL), and volume of distribution (V) of theophylline in premature neonates during the first few days after birth, and to identify factors contributing to interindividual variability. The authors obtained 263 serum concentrations from 105 apneic premature neonates receiving intravenous (IV) theophylline. Mean (SD) birth weight and postnatal ages were 1.3 (0.3) kg and 1.1 (0.3) days, respectively. The data were analyzed using the nonlinear mixed effects model (NONMEM). A one-compartment model with first order elimination was used. The final models were: CL (L/h) = 0.006 * WGT 0.75 * P, V (L) = 0.63 * WGT, WGT = weight (kg) P = 1.47 with oxygen support and 1.0 without oxygen support. The CL in the study population was low, resulting in long half-lives. After inclusion of the above covariates, as well as interoccasion variability, the interindividual variability in CL was 56% and in V was 47%. Interoccasion variability in CL and V was 34% and 35% respectively. Theophylline pharmacokinetics are variable in the premature neonate during the first week of life, and this high variability makes it difficult to predict drug concentrations with the same degree of accuracy as in other populations.

Thiazide diuretics, which are often prescribed to treat mild to moderate hypertension, commonly cause an increase in urinary zinc (Zn) excretion. Metabolic interrelationships between Zn and copper (Cu) are known to exist; consequently, Zn might influence Cu levels. This study aims to determine whether or not Cu and Zn levels in hypertensive patients were influenced by treatment with clopamide, a thiazide diuretic. Eight male patients, aged 36-59 and with an average supine diastolic pressure of 95-115 mm Hg, were treated with single daily doses of clopamide 5 mg as monotherapy for 16 weeks. Plasma, erythrocyte (RBC), and mononuclear leukocyte (WBC) levels of Cu and Zn were determined immediately before therapy (week 0) and again at weeks 8 and 16. There was a significant fall in Cu in mononuclear WBCs from 13.25 (SEM = 0.86) to 1.9 fg/cell (SEM = 0.56) (p less than 0.001) and an increase in Zn from 33.87 (SEM = 3.7) to 70.8 fg/cell (SEM = 11.7) (p less than 0.001), with no change in either cell count or measurable cell volume. Plasma Cu levels increased significantly (p less than 0.001), but the Zn levels decreased only slightly (p less than 0.03). Changes in RBC Cu levels during the treatment period were not significantly altered (p less than 0.1). Zn levels in RBCs were significantly (p less than 0.04) lower. It is concluded that treatment with clopamide may induce some changes in Cu and Zn levels in normal hypertensives, particularly in WBCs. Further investigation is needed to determine the extent of this influence.

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