ABSTRACT
Continuous renal replacement therapy (CRRT) is a common technique in critically ill patients. However, there is no uniformity in the pharmacokinetics of ciprofloxacin (CPFX) used during CRRT. The aims of the present study were to estimate the pharmacokinetics of CPFX and to determine the appropriate administration of CPFX for critically ill patients undergoing CRRT. The pharmacokinetics of ciprofloxacin total clearance (CL(tot)) was calculated based on the creatinine clearance (CL(cre)), dialysate flow (QD), and ultrafiltrate flow (QF) as follows: CL(tot(L/h)) = (4.83 CL(cre(L/h)) + 6.41) + 0.92 (QD + Q(F(L/h))) based on in vitro study using CRRT circuit model. We administered CPFX to critically ill patients based on the CL(tot), which was 50 x CL(tot(L/h)) (mg/day). We confirmed that the CPFX concentrations reached higher than optimal concentrations, and infection was successfully controlled in these patients.
Subject(s)
Anti-Infective Agents/pharmacokinetics , Ciprofloxacin/pharmacokinetics , Renal Replacement Therapy , Adult , Aged , Area Under Curve , Humans , Male , Pilot ProjectsABSTRACT
Critically ill patients often have complications of acute renal failure induced by severe infection or sepsis. The patients need administration of broad-spectrum antibiotics as well as continuous renal replacement therapy (CRRT). However, there is no uniform pharmacokinetics of antibiotics during the CRRT because CRRT is performed with the various combinations of dialysate flows (QD) and ultrafiltrate flows (QF). The aims of this study were to estimate the pharmacokinetics of panipenem/beta Mipron (PAPM/BP) and to determine the appropriate treatment regimens for PAPM/BP in critically ill patients undergoing CRRT. In patients with CRRT, the PAPM total clearance (PAPM CLtot) was calculated as the sum of PAPM clearance dependent on the living body and CRRT and shown as follows:PAPM CLtot (ml/min) = (1.2 CLcre + 66.5) + 0.86 (QD + QF) where CLcre is creatinine clearance. Pharmacokinetic values of PAPM were measured in 4 patients with CRRT. According to these results, the most appropriate treatment regimen regarding PAPM CLtot (ml/min) showed as follows:PAPM CLtot < 80 0.5 g every 12 hours or 1 g every 15 hoursPAPM CLtot 80 to 120 0.5 g every 8 hours or 1 g every 12 hoursPAPM CLtot 120 to 160 0.5 g every 6 hours or 1 g every 8 hours.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Critical Care , Organic Anion Transporters/antagonists & inhibitors , Renal Replacement Therapy/methods , Thienamycins/pharmacokinetics , Acute Kidney Injury/therapy , Adolescent , Aged , Anti-Bacterial Agents/administration & dosage , Body Height , Body Weight , Computer Simulation , Creatinine/blood , Creatinine/urine , Critical Illness , Female , Humans , Infusions, Intravenous , Male , Metabolic Clearance Rate , Pilot Projects , Thienamycins/administration & dosageABSTRACT
Monocarboxylate transporter (MCT), which cotransport L-lactic acid and protons across cell membranes, are important for regulation of muscle pH. However, it has not been demonstrated in detail whether MCT isoform contribute to the transport of L-lactic acid in skeletal muscle. The aim of this study was to characterize L-lactic acid transport using an human rhabdomyosarcoma (RD) cell line as a model of human skeletal muscle. mRNAs of MCT 1, 2 and 4 were found to be expressed in RD cells. The [14C] L-lactic acid uptake was concentration-dependent with a Km of 1.19 mM. This Km value was comparable to its Km values for MCT1 or MCT2. MCT1 mRNA was found to be present markedly greater than that MCT2. Therefore, MCT1 most probably acts on L-lactic acid uptake at RD cells. [14C] L-Lactic acid efflux in RD cells was inhibited by alpha-cyano-4-hydroxycinnamate (CHC) but not by butyric acid, a substrate of MCT1. Accordingly, MCT2 or MCT4 is responsible for L-lactic acid efflux by RD cells. MCT4 mRNA was found to be present significantly greater than that MCT2. We conclude that MCT1 is responsible for L-lactic acid uptake and L-lactic acid efflux is mediated by MCT4 in RD cells.
