The pharmacokinetics of ticarcillin/clavulanate acid in neonates.

The pharmacokinetics of a 25:1 combination of ticarcillin and clavulanate were studied in nine pre-term and seven full-term neonates. Pre-term neonates with a gestational age ranging from 30 to 36 weeks received 83.3 mg of ticarcillin and 3.3 mg of clavulanate per kg bw and full-term neonates with a gestational age from 39 to 43 weeks received 100 mg of ticarcillin and 4 mg of clavulanate per kg bw 8-hourly, each by a slow infusion over 10 min. Serum was sampled 15, 30, 60, 120, 240 and 480 min after the first dose and trough samples were additionally obtained on the fourth day of treatment. The patients were allocated to Groups 1-3 on the basis of the pharmacokinetic characteristics obtained. Group 1 comprised seven full-term babies. Group 2 contained seven pre-term neonates with a birth weight between 1915 and 2650 g and Group 3 consisted of two pre-term neonates of low birth weight (1400 g and 1640 g). Mean (+/- S.E.) pharmacokinetic characteristics of Group 1 patients for ticarcillin were: Cmax = 404.9 mg/l (36.0); T = 2.68 h (0.23); AUC = 1287 h.mg/l (69); Vd = 266 ml/kg (28) and for clavulanate: Cmax = 15.0 mg/l (1.2); T = 1.39 h (0.12); AUC = 30.1 h.mg/l (1.7); Vd = 263 ml/kg (22). Corresponding parameters for Group 2 patients for ticarcillin were: Cmax 278.7 mg/l (30.4); T = 4.20 h (0.49); AUC = 1107 h.mg/l (57); Vd = 338 ml/kg (35) and for clavulanate: Cmax = 8.4 mg/l (0.56); T = 2.56 h (0.18); AUC = 27.1 h.mg/l (2.0); Vd = 414 ml/kg (29). Drug accumulation was not observed in patients of Groups 1 and 2. Each of the two patients of Group 3 presented a pharmacokinetic profile which was considerably different from those observed in Groups 1 and 2. While in patients of the latter group the peak serum concentrations were achieved at 15-30 min after the end of infusion, these concentrations occurred between 120 and 240 min in one of the Group 3 patients. In the other Group 3 patient a remarkable drug accumulation was noted but was not associated with clinical or laboratory evidence of toxicity. These data show that ticarcillin and clavulanic acid in these dose ranges achieved adequate peak and trough concentrations in pre-term and full-term neonates.

[Pharmacokinetic and clinical studies with sisomicin in paediatrics (author's transl)]. / Pharmakokinetische und klinische Untersuchungen mit Sisomicin in der Pädiatrie.

Pharmakokinetic and clinical investigations were carried out with sisomicin, one of the newer aminoglycoside antibiotics, in 40 children aged from seven days to ten years. Serum concentrations were determined in 35 children 1/2, 1, 2, 4 and 6 hours after i. m. injection of 1.0 mg sisomicin/kg body weight. The average peak serum levels were 2.48 mg/l in children under three months and 3.58 mg/l in children between seven months and ten years. Renal elimination in newborns is delayed in comparison to older infants and children; the distribution volume of the central compartment diminishes with increasing age. The effect of these two counteracting tendencies is that renal clearance remains constant in the age groups investigated, however the frequency of drug administration must be adjusted according to age. During an average treatment period of ten days adequate serum concentrations between 3.1 mg/l and 6.2 mg/l one hour after injection could be achieved with dosages adjusted to age and body weight. Clinical results were good: 18 out of 20 children could be cured clinically, and 20 out of 21 isolated infectious agents were eliminated. There were no problems in local and systemic tolerance.