Pharmacokinetic of amikacin given intramuscularly in infected-CAPD patients

Abstract

The objective of this study was to determine pharmacokinetic parameters of amikacin administered by intramuscular route (IM) in infected-CAPD patients, to evaluate whether or not the amikacin concentration in plasma and dialysate within 48 hours following the drug administration could achieve the therapeutic level and whether or not its trough plasma concentration was in the range that claimed to be safe for ototoxicity and to determine the relationship between plasma and dialysate of amikacin concentrations following IM route of administration. Twelve patients who participated in this study performed CAPD four exchange per day with six hours dwell period. Of the 12 infected-CAPD patients, seven patients had peritonitis (58.3%) and five patients had catheter-related infection with no peritonitis (41.7%). The patients received only one dose of IM amikacin 7.5 mg/kg along with continuous IP cefazolin as an empirical treatment. Both plasma and dialysatesamples from the patients were collected within 48 hours. The results showed that all patients had peak plasma concentration of amikacin in the therapeutic range (15-30 mg/L) with the mean peak concentration equaled to 25.3 mg/L and the mean time to peak was at 2.6 hour. The trough plasma concentration of amikacin at 48 hours in all patients were higher than 5 mg/L with the mean concentration equaled to 10.3 mg/L which may cause ototoxicity if this dosage would be given every 48 hours. The mean volume of distribution was 35.99 L (0.56 L/kg), the mean total body clearance was 0.64 L/hr (10.73 ml/min) with the mean half-life approximately 38 hours. The mean peritoneal amikacin clearance was 0.23 L/hr (3.90 ml/min). Approximately 54% of the dose of amikacin administered was removed by CAPD. Amikacin concentration in dialysate showed the peak concentration every six hours at the end of each dialysate exchange and the maximum peak dialysate was found at the end of the first dialysate bag with the mean equaled to17.6 mg/L which was slightly higher than therapeutic concentration (>=16 mg/L) recommended by the United States' National Committee for Clinical Laboratory Standards (NCCLS). There was relationship between amikacin concentration in the plasma and in the dialysate. In conclusion, intramuscular administration of amikacin with the single dose of 7.5 mg/kg every 48 hours for the treatment of peritonitis in CAPD patients might not be an appropriate dosage regimen since the dialysate concentrations were mostly too low to be effective while the trough concentration in plasma was too high resulting in high risk of ototoxicity. However, the amikacin concentrations in dialysate could be used to derive the pharmacokinetic parameters which could then be used to predict the amikacin concentrations in plasma or vice versa. Further study should be continued.