The pharmacokinetics of colistin in patients with cystic fibrosis

The safety and pharmacokinetics of colistin were determined after first dos e (n = 30) and again under steady-state conditions (n = 27) in 31 patients with cystic fibrosis receiving the drug as a component of their treatment f or an acute pulmonary exacerbation of their disease. Patients ranged in age from 14 to 53 years end received colistin for 6 to 35 days. Each patient w as started on colistin 5 to 7 mg/kg/day administered intravenously in three equally divided doses. Elimination half-life (t(1/2), mean residence time (MRT), steady-state volume of distribution (Vd(ss)) total body clearance (C l) and renal clearance (Clr) after first-dose administration averaged 3.4 h ours, 4.4 hours, 0.09 l/kg, and 0.35 and 0.24 ml/min/kg, respectively. No d ifferences in colistin disposition characteristics between first-dose and s teady-state evaluations were observed. Sputum sampling was incomplete and c onfounded by previous aerosol administration but revealed colistin concentr ations that markedly exceeded observed plasma concentrations. Twenty-one pa tients experienced one or more side effects attributed to colistin administ ration. The most common reactions involved reversible neurologic manifestat ions, including oral and perioral paresthesias (n = 16), headache (n = 5), and lower limb weakness (n = 5). Ah of these apparent colistin-induced neur ologic adverse effects, though bothersome, were benign and reversible. Inte rmittent proteinuria was observed on urinalysis in 34 patients, and 1 patie nt developed reversible, colistin-induced nephrotoxicity. No relationship b etween the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetic parameter estimate was o bserved. These data provide no basis for routine monitoring of colistin pla sma concentrations to guide dosing for patient safety and suggest slow upwa rd dose titration to minimize the incidence and severity of associated side effects.