Clinical Pharmacokinetics of Sisomicin: Dosage Schedules in Renal-Impaired Patients

The pharmacokinetics of netilmicin were examined in 25 adult subjects, 7 normal subjects, and 18 patients with renal impairment. Five were dialysis patients who were studied on and off dialysis. Netilmicin, 2 mg/kg, was infused intravenously over 1 h. The peak serum concentration ranged from 9 to 11 μg/ml. The mean biological half-life of netilmicin for subjects with a creatinine clearance (Ccr) > 70 ml/min was 2.7 h, for those with Ccr > 25 < 70 ml/min it was 10 h, for those with Ccr > 4 < 25 ml/min it was 32 h, and for those who were anephric it was 42 h. Ccr was correlated positively with the elimination constant and the drug's serum clearance. It was negatively correlated with the drug's volume of distribution. The dialyzer clearance of netilmicin was positively correlated with plasma flow rate and was similar to values previously reported for gentamicin. Netilmicin behaves in a fashion similar to other aminoglycosides. Therapeutic guidelines are suggested.

supporting

confidence: 73%

supporting

confidence: 60%

See 1 more Smart Citation

Pharmacokinetics of Netilmicin in Patients with Renal Impairment and in Patients on Dialysis

Luft

Brannon

Stropes

et al. 1978

“…Previous pharmacokinetic data of sisomicin in adult volunteers and patients are similar to those described herein for children (3,8,11,12). Four subjects had extremely rapid tl/2 (<1 h), and this may indicate that age and/or health status have some influence on the elimination rate of this drug.…”

Section: Discussionsupporting

confidence: 55%

Clinico-Pharmacological Studies of Sisomicin in Ill Children

Marks

Vose

Hammerberg

et al. 1978

Sisomicin, at 4.5 mg/kg per day, was prescribed for the therapy of serious bacterial infections of hospitalized infants, children, and adolescents. Eleven children received full treatment courses, with 10 clinical and 9 bacteriological cures. Three patients with underlying disease (two cystic fibrosis and one aplastic anemia) accounted for the failures. Mean half-life was 98.3 min (range, 26.1 to 159.3), and peak serum concentrations 10 min after intravenous infusion were similar (5 to 6 ,g/ml) on days 1, 3, and 5 of therapy. Mean urinary concentrations were 54.3 isg/ml; 31 to 47% of the drug was excreted within the 8-h dosage interval.The drug was tolerated well by all patients; however, one patient, receiving the longest duration of therapy (26 days), developed reversible nephrotoxicity.The emergence of gentamicin-resistant bacteria in hospitalized patients has emphasized the importance of evaluating alternative antibiotics. Sisomicin is a new aminoglycoside antibiotic derived from the fermentation broth of Micromonospora inyoenis that has many properties in common with gentamicin as well as the advantage of activity against selected gentamicinresistant bacteria (4,6,9,14). The purpose of this study was to examine some of the pharmacokinetic, clinical, and toxicological properties of sisomicin in the therapy of serious infections of children. MATERIALS AND METHODSSisomicin was administered to 12 patients hospitalized at the Montreal Children's Hospital. These patients were selected by the attending physician as candidates for aminoglycoside therapy using standard clinical and laboratory criteria. Once a patient was selected to receive aminoglycosides, sisomicin was offered in lieu of gentamicin after carefully explaining the nature of the study and the differences between the two drugs to the parents and only after obtaining informed consent. Appropriate bacterial cultures and base-line laboratory studies were obtained in each case. When positive cultures were obtained before therapy, appropriate cultures were repeated during and after therapy as well. Sisomicin was administered in a dosage of4.5 mg/kg per day intravenously (divided every 8 h) over 0.5 h, and the duration of treatment was determined by standard clinical and bacteriological criteria.All patients were carefully examined for tolerance to the drug and for hematological, hepatic, and renal toxicities by the following tests: hemoglobin, hematocrit, white blood count and differential, platelets, serum glutamic oxaloacetic transa inase, bilirubin, alkaline phosphatase; urea nitrogen, creatinine, and urinalysis. These tests were carried out before, during, and after therapy.Audiological evaluations were performed within 72 h of initiation of therapy, and again after completion of the course of sisomicin. School-age children were studied by standard pure-tone and standard speech audiometry and impedance testing, pre-school children and infants by behavioral observation, play, and conditioned orienting response audiometry, and impedance measurements when...

“…Elimination of isepamicin is similar to that of other aminoglycoside antibiotics in that it is a function of the glomerular filtration rate (2,4,6,18,19). tHowever, compared with that of netilmicin (9), the Xz of isepamicin is significantly larger.…”

Section: Discussionmentioning

confidence: 85%

Isepamicin disposition in subjects with various degrees of renal function

Halstenson

Kelloway

Affrime

et al. 1991

The disposition of isepamicin, an investigational aminoglycoside antibiotic, was evaluated in 30 subjects with various degrees of renal function. The subjects were divided into five groups: those with normal renal function (creatinine clearance [CLCR] >80 ml/min/1.73 mi2), those with mild renal insufficiency (CLCR, 50 to 80 ml/min/ 1.73 m2), those with moderate renal insufficiency (CLCR, 30 to 49 ml/min/1.73 m2), those with severe renal insufficiency (CLCR, 5 to 29 ml/min/1.73 m2), and those maintained on hemodialysis (CLCR, <5 ml/min/1.73 m2).Subjects on hemodialysis were studied both during hemodialysis and during an interdialytic period. The volumes of distribution of isepamicin were not significantly different among the five groups of patients. The total body clearance (CLp) and renal clearance (CLR) of isepamicin significantly decreased as CLCR decreased. The CLp of isepamicin and CLCR were significantly related {(CLp = 0.391-[CLCRJ + 1.83; r2 = 0.878)}. Nonrenal clearance of isepamicin did not differ between groups. Hemodialysis augmented the CLp of isepamicin by -25-fold. The amount of isepamicin recovered in the dialysate was 60.6 ± 15.8% of the dose administered. The maximal rebound of the isepamicin concentration in plasma after cessation of hemodialysis was observed at 0.78 ± 0.7 h. Concentrations in plasma increased 32.7 ± 22.9% over that measured at the end of hemodialysis. These data indicate that dosage adjustments are necessary in subjects with decreased renal function.