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Jean Sebastien Hulot

Publications and source records attributed to Jean Sebastien Hulot.

4 recordsLinked to original sources
PubMed2005

Population pharmacokinetics of tacrolimus in full liver transplant patients: modelling of the post-operative clearance.

OBJECTIVE: To investigate the population pharmacokinetics of tacrolimus in an adult liver transplant cohort using routine drug monitoring data and to identify patient characteristics that influence pharmacokinetic parameters. METHODS: Tacrolimus pharmacokinetics was studied in 37 adult patients using a population approach performed with NONMEM. RESULTS: A one-compartment open model with linear absorption and elimination adequately described the data. The apparent clearance (CL) was approximately zero in the immediate post-operative days (PODs) and then rapidly increased as a function of POD to reach a plateau. This was modelled as a sigmoid relationship with the characteristic parameters CL(max) (plateau), TCL(50) (time to obtain 50% of the plateau) and gamma (coefficient of sigmoidicity). This clearance model was thought to describe the hepatic function regeneration after transplantation. Typical population estimates (percentage inter-individual variability) of CL(max), TCL50, and gamma and apparent distribution volumes (V) were 36 l/h (43%), 6.3 days (33%), and 4.9 l and 1870 l (49%), respectively. The CL(max) was negatively related to plasma albumin, and TCL50 was positively related to aspartate amino transferase (ASAT). Bayesian estimations performed at different POD times indicated that acceptable precisions in individual pharmacokinetic predictions could be obtained after the 15th POD. CONCLUSION: Tacrolimus clearance modelling showed that there was a large variation in individual CL estimates up to the 15th day post-surgery. After this period, the mean error resulting from the Bayesian estimation was strongly decreased and this estimation method could be applicable and should limit tacrolimus monitoring.

Bayes Theorem↗
PubMed2005

Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) was developed for the treatment of human immunodeficiency virus (HIV) infection. However, controlled data are sparse on the long-term renal tolerability of TDF at the currently approved daily dose of 300 mg in treatment-naive HIV-infected patients. METHODS: Over 144 weeks, this 600 patient, multicentre randomized, placebo-controlled, double-blind trial compared stavudine (301 patients) and TDF (299 patients), both administered in combination with lamivudine and efavirenz, in antiretroviral-naive patients. TDF or placebo and stavudine or placebo were administered in an open-label fashion. All medications were taken orally. At screening, all patients had serum creatinines <1.5 mg/dl, calculated creatinine clearances > or =60 ml/min and a serum phosphorus > or =2.2 mg/dl. RESULTS: The incidences of grades 1 (> or =0.5 mg/dl increase from baseline), 2 (2.1-3.0 mg/dl) and 3 (3.1-6.0 mg/dl) serum creatinine elevations at week 144 were 4, <1 and 0%, respectively, in the TDF group and 2, 0 and <1% in the stavudine control group (P = NS). There were no grade 4 (>6 mg/dl) serum creatinine elevations. At week 144, there was no change from baseline in the mean (0.83 mg/dl) serum creatinine in the TDF group compared with a 0.1 mg/dl decrease from baseline (0.83 mg/dl) in the stavudine control group. The incidences of grades 1 (2.0-2.2 mg/dl), 2 (1.5-1.9 mg/dl) and 3 (1.0-1.4 mg/dl) hypophosphataemia at week 144 were 4, 3 and <1%, respectively, in the TDF group and 4, 2 and <1% in the control group (P = NS). No patient experienced grade 4 (<1.0 mg/dl) hypophosphataemia. At week 144, the decrease (Delta) of mean serum phosphorus levels from baseline in both groups was similar (Delta 0.2 from 3.6 mg/dl for the TDF group, and 0.1 from 3.5 mg/dl for the stavudine control group). No patient developed Fanconi's syndrome or proximal renal tubular dysfunction during the study. CONCLUSION: Through 144 weeks, TDF and stavudine, each administered in combination with efavirenz and lamivudine, had similar renal safety profiles in treatment-naive HIV-infected patients with normal renal function at baseline.

Adenine↗
PubMed2004

Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies.

BACKGROUND: The incidence of adefovir dipivoxil (ADV) nephrotoxicity has been previously reported with the 60 and 120 mg daily dose in human immunodeficiency virus (HIV). We report a complete analysis on the renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B. METHODS: To investigate the efficacy, safety, and the tolerability of two dosing regimens of ADV (10 mg daily or 30 mg daily), two double-blind, placebo-controlled studies were performed in patients with chronic hepatitis B and compensated liver disease who were not undergoing current treatment and who had evidence of hepatitis B virus (HBV) replication. RESULTS: There was no overall median change from baseline at week 48 in serum creatinine or serum phosphorus levels in the ADV 10 mg group. In the ADV 30 mg group there was a slight increase of 0.2 mg/dL in median serum creatinine levels, and decrease of 0.1 mg/dL in serum phosphorus levels at week 48. Serum creatinine increase and hypophosphatemia were more frequently observed in patients receiving ADV 30 mg daily compared with ADV 10 mg and placebo. There were no grade 4 proteinuria, hematuria, or glycosuria events. CONCLUSION: Mild nephrotoxicity was demonstrated with the dose of 30 mg daily. Nephrotoxicity, as defined by an increase >/=0.5 mg/dL from baseline in serum creatinine or a serum phosphorus value of <1.5 mg/dL on two consecutive occasions, was not observed in patients treated with ADV 10 mg for a median follow-up period of approximately 64 weeks.

Adenine↗