Pharmacokinetics of habekacin in patients with renal insufficiency

Abstract

The pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic, were investigated in six healthy subjects and 25 uremic patients (six of whom were on hemodialysis) after administration of a single 3-mg/kg dose. Six healthy subjects received the 3-mg/kg dose both intramuscularly (i.m.) and intravenously (i.v.) (1-h infusion). Uremic patients were given the 3-mg/kg dose as an i.m. injection, except for the hemodialysis patients, who received the dose as a 1-h i.v. infusion. Afther the i.m. injection, the peak concentrations in serum were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. The elimination half-life in serum increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearances of less than 10 ml/min.

Population Pharmacokinetics of Arbekacin in Patients Infected with Methicillin-Resistant Staphylococcus aureus

“…Similar to other aminoglycosides, arbekacin is excreted exclusively in urine in its unchanged form via glomerular filtration, and some portion is reabsorbed by tubular reabsorption. In subjects with normal renal function receiving a single intramuscular dose of 3 mg/kg of body weight (typical half-life of arbekacin is 1.5 to 2.7 h), the apparent volume of distribution (V) is 0.28 to 0.37 liter/kg, and the total body clearance (CL) is 97 to 146 ml/min per 1.73 m 2 (6). In patients with severe renal insufficiency (creatinine clearance [CL CR ], Ͻ10 ml/min), the half-life is 18.5 to 46.4 h, the apparent V is 0.26 to 0.56 liter/kg, and total body CL is 8 to 12 ml/min per 1.73 m 2 (6).…”

Pharmacokinetic-Pharmacodynamic Relationship of Arbekacin for Treatment of Patients Infected with Methicillin-Resistant Staphylococcus aureus

“…As with other aminoglycosides, arbekacin is eliminated exclusively into the urine as the unchanged form via glomerular filtration and tubular reabsorption. There is a linear relationship between arbekacin pharmacokinetics and the glomerular filtration rate (4).…”

Pharmacokinetic (PK) Characteristics in Critically Ill Patients

“…Furthermore, such antibiotic adjustment has been performed even in patients with acute renal dysfunction followed by the conventional regulation [7]. Interestingly, V d in chronic renal failure patients does not increase in contrast to patients with acute renal dysfunction, as previously reported [8,9]. Thus, in critically ill patients with acute renal dysfunction, there would be certain differences in antibiotic dosing with those of chronic renal insufficiency.…”

“…Furthermore, such antibiotic adjustment has been done even in patients with acute renal dysfunction by the conventional regulations [7]. However in chronic renal failure patients, the distribution volume of ABK does not elevate in contrast to that of those with acute renal failure [8,9,10].…”

“…However, chronic renal failure patients have normal distribution volume of ABK [8,9,10] as well as other aminoglycosides [13]. The CL of ABK correlates significantly with CCR in patients with chronic renal failure [8].…”