RESUMO
The single-dose pharmacokinetics of ticarcillin and clavulanic acid (Timentin) were evaluated in children and young adults with cystic fibrosis after a 0.5-hour intravenous infusion of both a 3.1 and a 3.2 gm formulation (representing 3.0 gm ticarcillin combined with 100 mg and 200 mg clavulanic acid, respectively) in a crossover design. A 75 mg/kg dose of the ticarcillin component was used. Model-dependent and noncompartmental pharmacokinetic parameters were congruous. The disposition of ticarcillin and clavulanic acid was characterized adequately by a one-compartment open model. The elimination half-life, apparent steady-state volume of distribution, and total body clearance of ticarcillin from serum were 1.19 hours, 0.231 L/kg, and 0.150 L/hr/kg, respectively, for the 3.1 gm formulation and 1.21 hours, 0.211 L/kg, and 0.123 L/hr/kg, respectively, for the 3.2 gm formulation. For ticarcillin, 86% and 93% of the dose of the 3.1 and 3.2 gm formulations, respectively, were excreted unchanged in urine during the first 6 hours after infusion. Concomitant renal clearance values were 0.120 and 0.112 L/hr/kg for the 3.1 and 3.2 gm formulations, respectively. Approximately 50% of a clavulanic acid dose was excreted unchanged in urine during the 6-hour postinfusion period for both formulations. For ticarcillin, no significant differences were observed between the 3.1 and 3.2 gm formulations. For clavulanic acid, a significant difference between the two formulations was observed in comparison of the area under the serum concentration vs time curve and dose size (P less than 0.01). Linear inverse relationships were identified between demographic factors (e.g., age, weight, height, body surface area) and both the apparent volume of distribution and total body clearance of ticarcillin and clavulanic acid for both formulations. The ticarcillin/clavulanic acid combination in either the 3.1 or 3.2 gm formulation is suitable for microbiologic and clinical evaluation in patients with cystic fibrosis.
Assuntos
Antibacterianos/metabolismo , Ácidos Clavulânicos/metabolismo , Fibrose Cística/tratamento farmacológico , Penicilinas/metabolismo , Ticarcilina/metabolismo , Adolescente , Adulto , Antibacterianos/uso terapêutico , Criança , Ácido Clavulânico , Ácidos Clavulânicos/uso terapêutico , Fibrose Cística/metabolismo , Feminino , Humanos , Cinética , Masculino , Ticarcilina/uso terapêutico , Distribuição TecidualRESUMO
The single-dose pharmacokinetics of imipenem (N-formimidoyl thienamycin) was evaluated in 13 pediatric patients (mean age 5.2 +/- 3.5 years). Imipenem was administered in combination with cilastatin as either a 10 mg/kg or 25 mg/kg dose (not to exceed 500 mg) over 15 minutes. Plasma disposition in children was best described by a two-compartment open model. The distribution phase was rapid (t1/2 lambda 1 = 0.18 hours) and was followed by a monoexponential elimination phase (t1/2 lambda 2 = 1.2 hours). The calculated value for the apparent volume of distribution (0.66 L/kg) was similar to that of total body water. The total plasma clearance was rapid (0.36 L/hr/kg). Direct proportionality was exhibited between administered dose and either resultant plasma concentration or area under the plasma concentration versus time curve. Comparison of imipenem plasma pharmacokinetic data derived from these children with data reported from adult subjects revealed disparities for both the apparent volume of distribution and plasma clearance. Based on preliminary pharmacokinetic simulations using parameters generated from our study, a 25.0 mg/kg dose of imipenem administered every 6 hours appears adequate for initiation of therapy in children.