Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation

INTRODUCTION: In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting. METHOD: Seven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m(2 )AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography. RESULTS: The mean (± standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 ± 1 hours, 19 ± 6 l, 2514 ± 212 mg/h per l, and 62 ± 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8–36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 ± 0.11 and 33.6 ± 4 mg/l, respectively. CONCLUSION: We conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF

Etude de l'interaction pharmacocinétique potentielle entre le valaciclovir et le tacrolimus chez les transplantés rénaux

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Etude des interactions médicamenteuses entre le SB-751689 et la rosuvastatine et entre le SB-751689 et le kétoconazole dans une population de femmes en post-ménopause

PARIS-BIUP (751062107) / SudocSudocFranceF

PHARMACOLOGIE DES FLUOROQUINOLONES DE TROISIEME GENERATION (ETUDE D'UNE INTERACTION PHARMACOCINETIQUE POTENTIELLE ENTRE LA GREPAFLOXACINE ET LA RIFAMPICINE (DES PHARMACIE HOSPITALIERE ET DES COLLECTIVITES))

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Stereoselective Rearrangement of (Trifluoromethyl)prolinols to Enantioenriched 3‑Substituted 2‑(Trifluoromethyl)piperidines

3-Substituted 2-(trifluoromethyl)­piperidines <b>B</b> were synthesized by ring expansion of (trifluoromethyl)­prolinols <b>A</b>, which were obtained from l-proline via an aziridinium intermediate <b>C</b>. The ring opening of the (trifluoromethyl)­aziridinium intermediate by different nucleophiles is regio- and diastereoselective

Steady-State Pharmacokinetics of Amprenavir Coadministered with Ritonavir in Human Immunodeficiency Virus Type 1-Infected Patients

The protease inhibitor (PI) ritonavir is used as a strong inhibitor of cytochrome P450 3A4, which boosts the activities of coadministered PIs, resulting in augmented plasma PI levels, simplification of the dosage regimen, and better efficacy against resistant viruses. The objectives of the present open-label, multiple-dose study were to determine the steady-state pharmacokinetics of amprenavir administered at 600 mg twice daily (BID) and ritonavir administered at 100 mg BID in human immunodeficiency virus type 1 (HIV-1)-infected adults treated with different antiretroviral combinations including or not including a nonnucleoside reverse transcriptase inhibitor (NNRTI). Nineteen patients completed the study. The steady-state mean minimum plasma amprenavir concentration (C(min,ss)) was 1.92 μg/ml for patients who received amprenavir and ritonavir without an NNRTI and 1.36 μg/ml for patients who received amprenavir and ritonavir plus efavirenz. For patients who received amprenavir-ritonavir without an NNRTI, the steady-state mean peak plasma amprenavir concentration (C(max,ss)) was 7.12 μg/ml, the area under the concentration-time curve from 0 to 10 h (AUC(0-10)) was 32.06 μg · h/ml, and the area under the concentration-time curve over a dosing interval (12 h) at steady-state (AUC(ss)) was 35.74 μg · h/ml. Decreases in the mean values of C(min,ss) (29%), C(max,ss) (42%), AUC(0-10) (42%), and AUC(ss) (40%) for amprenavir occurred when efavirenz was coadministered with amprenavir-ritonavir. No unexpected side effects were observed. As expected, coadministration of amprenavir with ritonavir resulted in an amprenavir C(min,ss) markedly higher than those previously reported for the marketed dose of amprenavir. When amprenavir-ritonavir was coadministered with efavirenz, amprenavir-ritonavir maintained a mean amprenavir C(min,ss) above the mean 50% inhibitory concentration of amprenavir previously determined for both wild-type HIV-1 isolates and HIV-1 strains isolated from PI-experienced patients. These data support the use of low-dose ritonavir to enhance the level of exposure to amprenavir and increase the efficacy of amprenavir