Cloxacillin absorption and disposition in cystic fibrosis

Spino, Michael; Chai, Roger P.; Isles, Alan; Thiessen, Jake J.; Tesoro, Angel M.; Gold, Ronald; MacLeod, Stuart

doi:10.1016/s0022-3476(84)80317-0

Cited by 68 publications

(32 citation statements)

References 20 publications

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“…This sug gests that there is similar renal clearance as well as plasma clearance in comparison to non-CF subjects. We found similar absor bance of probenecid in CF subjects and con trols as that found for other drugs, theophyl line [17] and cloxacillin [18].…”

Section: Total Body Clearancesupporting

confidence: 85%

Probenecid Pharmacokinetics in Cystic Fibrosis

Weber¹,

Groot²,

Ramsey³

et al. 1991

Dev Pharmacol Ther

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Probenecid pharmacokinetics were studied in 5 cystic fibrosis (CF) subjects and 5 control subjects at oral dosages of 5, 15, and 30 mg/kg. Serum and urine samples were collected for 8 h after administration and assayed by reverse phase high performance liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. All parameters were compared by 2-tailed analysis of variance with two major groupings: patient and dose. Both CF subjects and controls demonstrated dose-dependent kinetics, i.e., decreased elimination constant and decreased total body clearance with increasing dosage. The volume of distribution and time to peak were the only parameters that were not significantly dose dependent. At all dosages studied, we found no significant difference in total body clearance by CF subjects. Urinary recovery in an 8-hour period was not significantly different between CF subjects and controls nor was the percentage of dose recovered in the urine at each dosage level. Time to peak concentration varied widely between 0.5 and 4 h in both CF subjects and controls. We conclude, that CF patients have normal probenecid clearance, and that the standard dose for a CF patient is sufficient to attain a serum area under the curve equivalent to that of controls.

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Section: Total Body Clearancesupporting

confidence: 85%

Probenecid Pharmacokinetics in Cystic Fibrosis

Weber¹,

Groot²,

Ramsey³

et al. 1991

Dev Pharmacol Ther

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“…(Bergan & Michalsen, 1979;Jusko et al, 1974Jusko et al, , 1975Guggenbichler & Kienel, 1979;Yaffe et al, 1977;Spino et al, 1984). The cause of the discrepancy between these findings and our results is not clear.…”

Section: Plasma Drug Concentrationscontrasting

confidence: 59%

The tubular excretion of benzylpenicillin in patients with cystic fibrosis.

Bins

Mattie

1989

Brit J Clinical Pharma

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1 The tubular excretion of benzylpenicillin (BP) was investigated in six volunteers with cystic fibrosis. 2 The volunteers received a continuous infusion of BP at increasing infusion rates in order to maintain constant plasma concentrations at three different levels. Blood and urine samples were taken every 30 min. Sufficient urinary flow was ensured by a saline infusion (500 ml h-1).3 The renal clearance of BP was calculated for the non-protein bound fraction of the drug. 4 Tubular clearance and tubular excretion rate were estimated from the renal clearance of the antibiotic minus the glomerular filtration rate; the latter was considered to be equal to creatinine clearance.5 The data were analysed according to a Scatchard plot and values for ECU50 and maximal tubular excretion rate were calculated. The mean value of ECU50 was 89 ± 24 (mg 1-l ± s.d.) and that for the maximal tubular excretion rate was 2603 ± 714 (mg h-1 + s.d.).The latter value was significantly less than that found in a previous study of healthy volunteers, but the ECU50 was similar. 6 It is concluded that the tubular excretory capacity for BP is decreased in patients with cystic fibrosis in direct relation to their low body weight.

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“…Increased clearance and altered volume of distribution for aminoglycosides and beta-lactam antibiotics have been described in patients with CF as compared with normal subjects or non-CF children (11,12,15,25; L. Cliche, M. LeBel, and M. G. Bergeron, Can. J. Hosp.…”

mentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of ciprofloxacin in cystic fibrosis patients

LeBel¹,

Bergeron²,

Vallée³

et al. 1986

Antimicrob Agents Chemother

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The pharmacokinetics and blister fluid penetration of oral ciprofloxacin were compared in 11 cystic fibrosis (CF) patients who had sputum colonization but were asymptomatic and in 12 healthy volunteers after a single dose (500 mg) and at steady state (500 mg every 8 h). The antibacterial effect of ciprofloxacin therapy was also evaluated by bacterial counts of colonizing pathogens in the respiratory secretions of CF patients. The CF patients were 15.9% lighter in weight than the controls (P less than 0.05). After a single dose, the elimination half-life of ciprofloxacin was decreased by a third in the CF patients as compared with the controls (2.62 versus 3.93 h, respectively; P less than 0.01). This was the result of a diminished apparent volume of distribution in CF subjects. Interestingly, we observed no statistically significant difference in total apparent and renal clearances between the groups. Suction-induced blister fluid penetration was not different between CF patients and healthy volunteers. In CF patients, ciprofloxacin exhibited levels in respiratory secretions above the reported MIC for Pseudomonas aeruginosa: 1.36 and 1.86 micrograms/ml at 2 h after a single dose and at steady state, respectively. An important fall (mean, 3.9 log10/ml) in the log titer in 10 patients with P. aeruginosa in their respiratory secretions was observed after 5 days of treatment. However, this improvement was short-lived; the secondary increase in bacterial counts observed in five patients and the development of five resistant strains were causes for concern. The pharmacokinetic results presented here showed that ciprofloxacin should be administered every 8 or even every 6 h in CF patients.

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Cloxacillin absorption and disposition in cystic fibrosis

Cited by 68 publications

References 20 publications

Probenecid Pharmacokinetics in Cystic Fibrosis

Probenecid Pharmacokinetics in Cystic Fibrosis

The tubular excretion of benzylpenicillin in patients with cystic fibrosis.

Pharmacokinetics and pharmacodynamics of ciprofloxacin in cystic fibrosis patients

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