Isepamicin disposition in subjects with various degrees of renal function

Halstenson, Charles E.; Kelloway, J S; Affrime, Melton B.; Lin, Chyi-Chyang; Teal, M A; Shapiro, Bruce E.; Awni, Walid M.

doi:10.1128/aac.35.11.2382

Cited by 13 publications

(7 citation statements)

References 19 publications

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“…However, it has been reported that increased plasma concentrations after hemodialysis can be observed for several antibiotics (5–7); therefore, the true rate of decrease, which should be considered the rebound in plasma concentration between the beginning and end of hemodialysis, was calculated. This value was obtained by dividing the difference between points B end and C 2 (point B before in Fig.…”

Section: Methodsmentioning

confidence: 99%

Removal of Doripenem During Hemodialysis and the Optimum Dosing Regimen for Patients Undergoing Hemodialysis

et al. 2011

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The removal of doripenem by hemodialysis was studied in six hemodialysis patients. Following an intravenous drip infusion of 0.5 g of doripenem, plasma concentrations of the drug were measured. The decrease in drug concentrations in plasma was observed during various periods of non-hemodialysis, and hemodialysis accelerated the elimination of doripenem. For example, the calculated mean half-life during hemodialysis was significantly shorter than that during non-hemodialysis periods (P = 0.002). The calculated pharmacokinetic parameters indicated that the mean rate of decrease in plasma concentration due to hemodialysis alone was 56.12 ± 8.11%. Upon obtaining these results and several pharmacokinetic parameters, we attempted to optimize the dosing regimen of doripenem for hemodialysis patients. We recommend the use of 0.25 g of doripenem once a day in patients infected with viable bacteria, and in patients who are infected with Pseudomonas aeruginosa, 0.5 g twice a day on the first day of administration, followed by 0.5 g once a day.

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Section: Methodsmentioning

confidence: 99%

Removal of Doripenem During Hemodialysis and the Optimum Dosing Regimen for Patients Undergoing Hemodialysis

et al. 2011

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“…An open twocompartment PK model with zero-order input was used to describe isepamicin kinetics. This choice was based on previous studies on the disposition of isepamicin (7). The four-dimensional vector of kinetic parameters consisted of the volume of distribution in the central compartment (V c ), CL, the distribution clearance (CL D ), which describes the exchange between the central and the peripheral compartments, and the volume of the peripheral compartment (V t ).…”

Section: Methodsmentioning

confidence: 99%

“…Isepamicin is a new semisynthetic aminoglycoside derived from gentamicin B whose resistance to aminoglycoside-inactivating enzymes is better than that of all the other available members of this family of antibiotics (5,20). Its pharmacokinetics (PK) have been studied in healthy volunteers (21), in patients with various degrees of renal insufficiency (7,24) or end-stage renal disease (8), and in children (11). Isepamicin PK were very similar to those of all of the other aminoglycosides related to gentamicin (13).…”

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confidence: 99%

Population pharmacokinetic study of isepamicin with intensive care unit patients

Tod

Padoin

Minozzi

et al. 1996

Antimicrob Agents Chemother

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The pharmacokinetics (PK) of isepamicin, a new aminoglycoside, were studied in 85 intensive care unit (ICU) patients and were compared with those observed in 10 healthy volunteers. A parametric method based on a nonlinear mixed-effect model was used to assess population PK. Isepamicin was given intravenously over 0.5 h at dosages of 15 mg/kg once daily or 7.5 mg/kg twice daily. The data were fitted to a bicompartmental open model. Compared with healthy volunteers, the mean values of the PK parameters were profoundly modified in ICU patients: elimination clearance was reduced by 48%, the volume of distribution in the central compartment (Vc) was increased by 50%, the peripheral volume of distribution was 70% higher, the distribution clearance was 146% lower, and the elimination half-life was ca. 3.4 times higher. The interindividual variability in PK parameters was about 50% in ICU patients. Five covariates (body weight [BW], simplified acute physiology score [SAPS], temperature, serum creatinine level, and creatinine clearance [CLCR]) were tentatively correlated with PK parameters by multivariate linear regression analysis with stepwise addition and deletion. The variability of isepamicin clearance was explained by three covariates (BW, SAPS, and CLCR), that of Vc was explained by BW and SAPS, and that of the elimination half-life was explained by CLCR and SAPS. Simulation of the concentration-versus-time profile for 500 individuals showed that the mean peak (0.75 h) concentration was 18% lower in ICU patients than in healthy volunteers and that the range in ICU patients was very broad (28.4 to 95.4 mg/liter). Therefore, monitoring of the isepamicin concentration is in ICU patients is mandatory.

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“…Previous work has detailed the disposition of isepamicin administered to patients with various degrees of renal function (10). On the basis of that study, a dosing adjustment of isepamicin based on the patient's creatinine clearance was proposed.…”

Section: * Corresponding Authormentioning

confidence: 99%

Effect of concomitant administration of piperacillin on the dispositions of isepamicin and gentamicin in patients with end-stage renal disease

Halstenson

Wong

Herman

et al. 1992

Antimicrob Agents Chemother

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Piperacillin inactivation of the aminoglycosides isepamicin and gentamicin in 12 chronic hemodialysis patients was assessed. Six subjects each received isepamicin (7.5 mg/kg of body weight) or gentamicin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Isepamicin and gentamicin concentrations in plasma and urine were monitored over 48 h after each dose and analyzed by highperformance liquid chromatography and fluorescence polarization immunoassay, respectively. The pharmacokinetics of isepamicin were not significantly altered during combination treatment with piperacillin. piperacillin (3.56 0.38 ml/min) increased significantly compared with that of gentamicin (2.03 0.50 ml/min) given alone. The results of this study suggest that no additional dosage adjustment of isepamicin during concomitant therapy with piperacillin in hemodialysis patients is necessary. However, this does not preclude the need for appropriately ex vivo-handled specimens for monitoring isepamicin concentrations in plasma to ensure therapeutic efficacy and prevent toxicity. Furthermore, additional dosage adjustments may be necessary when gentamicin is used concomitantly with piperacillin, on the basis of the significant in vivo inactivation that takes place in end-stage renal disease patients.

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Isepamicin disposition in subjects with various degrees of renal function

Cited by 13 publications

References 19 publications

Removal of Doripenem During Hemodialysis and the Optimum Dosing Regimen for Patients Undergoing Hemodialysis

Removal of Doripenem During Hemodialysis and the Optimum Dosing Regimen for Patients Undergoing Hemodialysis

Population pharmacokinetic study of isepamicin with intensive care unit patients

Effect of concomitant administration of piperacillin on the dispositions of isepamicin and gentamicin in patients with end-stage renal disease

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