Comparative Pharmacokinetics of BB-K8 and Kanamycin in Dogs and Humans

The pharmacokinetics of anmikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and nonnal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 mim produced concentrations in serum of 29.3 ± 5.7 jig/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 ± 1.7 jsg/ml and at 6 h of 1.2 ± 0.3 ,ug/ml. The serum half-life was 1.24 ± 0.09 h, volume of distribution was 0.26 ± 0.02 liter/kg, and total body clearance rate was 131 ± 10 ml/min per 1.73 m2. No accumulation of amnikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.

supporting

confidence: 50%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Amikacin pharmacokinetics in pediatric patients with malignancy

Cleary¹,

Pickering²,

Kramer³

et al. 1979

“…Particularly noteworthy is its effect against Pseudomonas aeruginosa and many gentamicin-resistant gram-negative bacilli (1,11,12). Amikacin is derived from kanamycin A and has pharmacokinetic characteristics that are similar to kanamycin (2,3), and animal experiments suggest that it may be comparable to kanamycin with respect to ototoxicity (9). Thus, when clinical trials at this medical center began, administration of the drug was accompanied by careful surveillance for ototoxic effects.…”

mentioning

confidence: 99%

Ototoxicity of Amikacin

Black

Lau

Weinstein

et al. 1976

121

Amikacin was used in 77 treatment courses at a dosage of ≥7.5 mg/kg every 8 h, and patients were monitored for ototoxicity by following serial audiograms, serum creatinine, and amikacin blood levels. Patients were leukopenic (58), were infected by gentamicin-resistant organisms (11), or had cystic fibrosis (8). Three patients developed tinnitus, but none had vertigo or nystagmus. Of 55 courses with pre- and post-treatment audiogram, 13 (24%) were associated with development of high-frequency hearing loss, which was usually bilateral. No patient had conversational hearing loss, and audiograms reverted to normal in three patients. Onset of cochlear damage occurred in one patient after therapy was stopped. The group with high-tone hearing loss, in comparison to the group without audiographic changes, received a larger mean total dose (24 versus 9.6 g), were treated for a longer duration (19 versus 9 days), and more frequently had previous aminoglycosides. Fifty-seven percent of patients with a “peak” serum level exceeding 32 μg/ml and 55% of patients with “trough” levels exceeding 10 μg/ml developed cochlear damage. There was no difference between the groups in age, body weight, previous cochlear damage, renal disease before or during therapy, or average daily dose. Both monitoring of blood levels and limiting duration of therapy may prevent amikacin ototoxicity.

“…the parent compound, kanamycin (3,4,7). The Therapy with amikacin was administered because antibacterial spectrum of amikacin is broader urological surgery was electively sceduled (cases 1, 3, than that of kanamycin, and includes many 4,9) or because febrile clinical illness was present (the sthains of kanamycin, an .nincues many remaining cases).…”

mentioning

confidence: 99%

Amikacin (BB-K8) Treatment of Multiple-Drug-Resistant Proteus Infections

Sharp

Saenz

Martin

1974

The new aminoglycoside antibiotic, amikacin (formerly called BB-K8), was used to treat 12 episodes of urinary tract infection caused by hospital-acquired Proteus rettgeri strains. These bacteria were resistant in vitro to kanamycin and gentamicin, and infection persisted in most of the patients in spite of therapy with one of these agents. In all cases, the urinary tract infection was controlled or eradicated by therapy, although relapse or reinfection was frequently encountered in these patients with complicated urological problems. No toxicities attributable to the drug were encountered in the small group of patients.Amikacin (formerly called BB-K8) is a new gested that a reservoir of infection might exist in the semisynthetic aminoglycoside antibiotic with hospital, epidemiological studies failed to reveal a pharmacological properties similar to those of definite common source for the P. rettgeri organisms. the parent compound, kanamycin (3, 4, 7). The Therapy with amikacin was administered because antibacterial spectrum of amikacin is broader urological surgery was electively sceduled (cases 1, 3, than that of kanamycin, and includes many 4, 9) or because febrile clinical illness was present (the sthains of kanamycin, an .nincues many remaining cases). Most of the patients had received strains of kanamycin-or gentamicin-resistant other antimicrobial therapy without effect on the Enterobacteriaceae and Pseudomonas (2, 4-6, urinary infection before amikacin was started. One 8, 9). Animal studies have indicated that ami-patient (patient 1) received a second course of amikakacin is potentially nephrotoxic and ototoxic cin therapy after a relapse of infection and when an and that it may produce neuromuscular block-additional surgical procedure was required. ade (7).Specimens for culture were collected and processedThe following report summarizes the use of in the diagnostic bacteriology laboratories of the Ben intramuscular amikacin in 11 patients with 12 Taub General Hospital. Pretreatment urine cultures episodes of infection. All of thesepatientsh of all patients with urinary tract infection contained episodes ot infection. A of these patients had greater than 100,000 colonies/ml. Bacteria were idenurinary tract infections caused by a hospital tified by standard bacteriological methods, and disk strain of Proteus rettgeri resistant to kanamycin sensitivity testing was performed by the Bauer-Kirby and gentamicin, and one of the patients was method (1). bacteremic. Patients were carefully monitored The P. rettgeri strains isolated from the patients in for renal, vestibular, and auditory toxicity, and this series were resistant by Bauer-Kirby disk no evidence of toxicity to amikacin was de-susceptibility testing to all antibiotics routinely tected.