azlocillin and Kidney-Failure--Chronic

Azlocillin is an important acylureido penicillin antibiotic for the management of complex gram-negative infections particularly those caused by Pseudomonas species. The current studies demonstrate that it manifests dose-dependent pharmacokinetics during the usual regimens of clinical dosing, that enterohepatic recirculation does not occur and that renal tubular secretion (maximum renal tubular secretory capacity 300 +/- 30 micrograms/min) and hepatic metabolism appear to be the dominant contributors to the dose-dependent nature of azlocillin. The possible therapeutic implications of azlocillin's dose dependency were evaluated by undertaking a six-day randomized, prospective, cross-over design study to evaluate the pharmacokinetic disposition of the drug during a 3-g q4h (typically used in adults) regimen versus a 5-g q8h regimen. By using the area under the serum-time concentration curve (AUC) as the major comparative parameter for these two regimens, the results demonstrate that both regimens provide approximately equal quantitative amounts of the drug systemically as a result of azlocillin's dose dependency. The AUC values, although not therapeutic end points, nonetheless correlate well with clinical response to antibiotic therapy. The 5-g q8h regimen was well tolerated. It is less disruptive for patients, requires half the number of intravenous administrations, 17% less drug, and is more cost effective than the 3-g q4h regimen.

Topics: Adult; Azlocillin; Female; Half-Life; Humans; Intestinal Absorption; Kidney Failure, Chronic; Kidney Tubules; Male

The pharmacokinetics of azlocillin were studied in 16 patients with varying degrees of renal impairment (creatinine clearance Ccr ranging from 0 to 52 ml/min/1.73 m2) and on and off sessions in 4 of these patients on periodical haemodialysis. A single dose of azlocillin 80 mg/kg was given by intravenous infusion over 30 min. Maximum concentrations in the sera of patients with renal impairment were the same as in normal subjects, ranging from 300 to 400 micrograms/ml. The elimination half-life (t 1/2) increased as renal function deteriorated, with values of 1.11 h in subjects with healthy kidneys to 5.66 h in patients with Ccr less than 15 ml/min (maximum 8.38 h). The apparent volume of distribution (Vd) was unchanged in patients with renal impairment but was significantly increased in patients on haemodialysis. The mean percentage of the dose administered excreted in the urines decreased from 60-70% in normal subjects to about 11% in patients with severe renal failure, but urinary concentrations remained above therapeutic levels. The extra-renal elimination of azlocillin was unmodified by renal impairment. Azlocillin is easily removed by dialysis: t 1/2 values between and during 6 h sessions of haemodialysis were 6.55 h and 2.81 h respectively, corresponding to a 45.8% extraction on the dialyser. These results are comparable to those found in the literature and can be used as a basis for adjusting azlocillin dosage to the degree of renal function.

Topics: Adolescent; Adult; Aged; Azlocillin; Female; Half-Life; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Penicillins; Renal Dialysis

The kinetic disposition of azlocillin in patients with end stage renal failure was evaluated in six individuals maintained on chronic extracorporeal haemodialysis and in six individuals on peritoneal dialysis. In the absence of renal function the plasma half-life of azlocillin was extended from the normal value of approximately 60 min to 235 +/- 30 min. During peritoneal dialysis the plasma half-life was reduced to 148 +/- 15 min and during extracorporeal haemodialysis it was further reduced to 112 +/- 11 min. Azlocillin was readily dialysed during haemodialysis but its removal rate during peritoneal dialysis was substantially less.

Topics: Adult; Aged; Azlocillin; Biological Assay; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Penicillins; Peritoneal Dialysis; Renal Dialysis

Topics: Adult; Aged; Anti-Bacterial Agents; Azlocillin; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections

Pharmacokinetic properties and clinical efficiency of azlocillin were investigated in three patients with terminal renal failure both during and without haemodialysis. All patients were treated for urinary tract infections with azlocillin 2 g three times daily for a period of ten days. Mean serum half-lives off dialysis were 251 min and on dialysis 202 min. Azlocillin clearances increased from a mean value of 58.7 ml/min off dialysis to 72.6 ml/min on dialysis. Urinary excretion of the total daily dose of azlocillin was less than 5% for all patients, but from day 2 onwards all patients had urine levels which were more than 8 times above the approximate MIC value of the infecting bacteria.

Topics: Aged; Azlocillin; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Penicillins; Renal Dialysis; Urinary Tract Infections

The kinetics of the antipseudomonas penicillin, azlocillin, was studied after intravenous injection in 9 patients with creatinine clearance under 7 ml/min. All were on long-term hemodialysis; 3 were also studied during a dialysis-free period. Kinetic parameters were derived using a 2-compartment open model. The mean serum azlocillin half-life (t 1/2) was 1.93 hr in patients on dialysis and approximately 5 hr off dialysis. Thirty percent of the dose was recovered in the dialysate during a 4-hr period. An approach to the use of azlocillin in patients undergoing dialysis is presented.

Topics: Adult; Azlocillin; Half-Life; Humans; Injections, Intravenous; Kidney Failure, Chronic; Kinetics; Models, Biological; Penicillins; Renal Dialysis

The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a single dose of 30 mg/kg in normal subjects, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T(1/2alpha)) was 0.11 h, and the mean elimination serum half-life (T(1/2beta)) was 0.89 h. The volume of the central compartment (V(C)) was 7.36 liters/1.73 m(2), and the apparent volume of distribution (V(dss)) was 14.15 liters/1.73 m(2), i.e., 21.9% of body weight. The T(1/2beta) after a 30-min intravenous infusion of 80 mg/kg to the same healthy subjects was 1.11 h. Serum clearances (C(S)) for the 30- and 80-mg/kg doses were 215.0 and 152.9 ml/min per 1.73 m(2). The mean renal clearances (C(R)) were 145.2 and 94.1 ml/min per 1.73 m(2) for the respective doses. Between 61.8 and 69.6% of the injected dose was recovered in urine during the first 24 h. The elimination half-life in subjects with chronic renal impairment increased with the degree of renal insufficiency. After a 30-min intravenous infusion of 80 mg/kg the T(1/2beta) values were 2.03, 4.01, and 5.66 h with creatinine clearances (C(cr)) within 30 to 50, 10 to 30, and <10 ml/min per 1.73 m(2), respectively. Urinary elimination was inversely related to the degree of renal impairment. In four patients out of and on a 6-h hemodialysis session mean elimination half-life values were 6.53 and 2.81 h, respectively. The fraction of drug removed by dialysis was 45.8%. The linear relationships between the elimination of half-life (T(1/2beta)) and serum creatinine and the elimination rate constant (beta) and creatinine clearance (C(cr)) provided a basis for adjustment of dosage in renal failure.

Topics: Adult; Azlocillin; Creatinine; Half-Life; Humans; Kidney Failure, Chronic; Penicillins; Renal Dialysis