Pharmacokinetics and tissue penetration of ceftazidime: studies on lymph, aqueous humour, skin blister, cerebrospinal and pleural fluid

Abstract

The elimination kinetics and penetration of ceftazidime into skin blister and lymphatic fluid were studied in nine healthy volunteers following a 1 g iv bolus injection. From the concentration time curve in plasma the following pharmacokinetic parameters (mean +/- S.D.) were calculated: elimination half-life 1.85 +/- 0.33 h; area under the curves 127 +/- 12 mg . h/l; apparent volume of distribution: 21.1 +/- 2.61; total plasma clearance: 133 +/- 13 ml/min and renal clearance: 109 +/- 7 ml/min. Urine recovery after 8 h was 82% of the administered dose. Nearly the same elimination rate constant, half-life and area under the curve were demonstrated for blister fluid and lymph. The penetration of ceftazidime into cerebrospinal fluid (n = 19), aqueous humour (n = 21) and pleural effusions (n = 5) were studied in patients after a 2 g iv bolus injection. In patients with normal meninges (n = 14) the penetration was poor: the concentrations were less than 1 mg/l. In patients with meningitis (n = 5) levels of 18, 17, 16, 1 and 0.8 mg/l were found. Aqueous humour penetration was satisfactory, and a mean concentration of 11 +/- 4 mg/l corresponding to a penetration ratio of 19% was found. The penetration of ceftazidime into large pleural effusions was also good with concentrations from 17 +/- 3 to 28 +/- 2 mg/l, corresponding to a mean penetration ratio of 38%.