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

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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/1. 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%.

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