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Biomedical subjects

R Boulieu

Publications and source records attributed to R Boulieu.

At least 55 records · Page 3Linked to original sources
PubMed1994

Pharmacokinetics of ganciclovir in a patient undergoing chronic haemodialysis.

The pharmacokinetics of ganciclovir was evaluated in a 73-year old anuric, haemodialyzed patient given 1.25 mg.kg-1 at the end of each haemodialysis session, three times per week. A biexponential decrease in plasma ganciclovir was observed, with a peak concentration of 3.7 mg.l-1 followed by a steady state value of 2.6 mg.l-1 for almost 40 h. The total plasma clearance was 0.05 ml.min-1.kg-1, the volume of distribution at steady state was 0.6 l.kg-1, the elimination half life was 132 h, the area under curve was 372 micrograms.h.ml-1, the mean residence time was 190 h, and the percentage of ganciclovir cleared from plasma after a 5 h haemodialysis session was 52.1%. The simulated pharmacokinetics over one month, following the same scheme of administration, did not suggest marked accumulation of ganciclovir. These results were obtained after a reduction of 58% in the recommended dose in patients with impaired renal function.

Aged↗
PubMed1994

Clinical use of ganciclovir during renal failure and continuous hemodialysis.

OBJECTIVE: Data is scarce concerning ganciclovir, used in CMV-related diseases in transplant patient with renal failure, especially when dialysis is necessary. DESIGN: Prospective trial. SETTING: Intensive care unit in a university hospital, and pharmacy laboratory. PATIENTS: pharmacokinetics were obtained in 3 patients undergoing continuous veno-venous hemodialysis (CVVHD) (PAN 69). INTERVENTIONS: HPLC measurements of plasmatic and ultrafiltrated ganciclovir were determined at 17 times intervals after a 5 mg/kg every 48 h dosage. RESULTS: Peak and trough concentrations were respectively 16.1 +/- 2.4 and 5.5 +/- 0.5 mg/l, sieving coefficient 0.75-0.95, and volume of distribution at steady state 0.64 +/- 0.09 l/kg, half life (beta phase) 18.6 +/- 1.8 h. No direct toxicity, or CMV-related death occurred. CONCLUSION: Plasma concentrations were higher than the ID 90. A dosage of 5 mg/kg/48 h of ganciclovir could be used during CVVHD, and ideally adjusted to monitoring of plasma drug levels.

Chromatography, High Pressure Liquid↗
PubMed1994

Effect of cardiopulmonary bypass on plasma concentrations of diltiazem and its two active metabolites.

Diltiazem is often used to prevent myocardial ischaemia during the perioperative period of coronary artery bypass surgery. The purpose of this study was to investigate the effect of cardiopulmonary bypass (CPB) on plasma concentrations of diltiazem and of its two main and active metabolites (N-monodemethyldiltiazem (N-desmethyldiltiazem) and desacetyldiltiazem). The patients were administered their usual treatment during the preoperative days. The last dose was administered immediately before anaesthesia. At the onset of CPB, a significant decrease in the plasma concentrations of diltiazem and its metabolites was observed, whereas the variation was slight and not significant when the plasma concentrations were corrected for haemodilution. These results confirm that the decrease observed at the initiation of the bypass procedure can be ascribed to the haemodilution induced by the CPB. During CPB, the concentrations of diltiazem and its metabolites remained constant suggesting that the rate of metabolism and excretion of the drug was altered during the bypass procedure. At the end of CPB, there was no increase of drug plasma concentrations suggesting that no redistribution of diltiazem from tissues to plasma occurred. Furthermore, this study shows that only 33% of subjects have therapeutic levels of diltiazem before anaesthesia, and that all subjects have subtherapeutic levels during and after the CPB. These results suggest that a higher chronic oral dose of the drug should be given in patients undergoing cardiac surgery with CPB.

Aged↗
PubMed1993

High-performance liquid chromatographic determination of thiopurine metabolites of azathioprine in biological fluids.

A selective and sensitive reversed-phase liquid chromatographic method for the analysis of thiopurine bases, nucleosides and nucleotides in biological samples was developed. A simple and rapid sample treatment procedure using perchloric acid deproteinization with dithiothreitol for the analysis of thiopurine bases and nucleosides is presented. The addition of dithiothreitol during sample collection and treatment improves recoveries. This procedure also allows the determination of thiopurine nucleotides by hydrolysis to their free bases after heating of the perchloric acid extract. The method was applied to the analysis of thiopurine metabolites in plasma and erythrocytes from lung-transplant patients under azathioprine therapy.

Azathioprine↗
PubMed1993

Comparison of the pharmacokinetics of methohexital during cardiac surgery with cardiopulmonary bypass and vascular surgery.

The aim of this study was to assess the pharmacokinetics of methohexital (ME) in major vascular surgery (VASC) and to compare these data with the pharmacokinetics of ME during hypothermic cardiopulmonary bypass (HCPB) (temperature: 28 degrees C) and normothermic cardiopulmonary bypass (NCPB) (temperature: 37 degrees C). An ME bolus (2 mg/kg) was administered to 8 VASC patients at the start of surgery and to 11 HCPB patients and 11 NCPB patients at the start of cardiopulmonary bypass (CPB). Twenty-one arterial blood samples were withdrawn over the following 24 hours for ME assays. All of the patients were given similar anesthesia (fentanyl, diazepam) and muscle relaxation (pancuronium). In the VASC group, ME total body clearance (TBC) was 6 +/- 2 mL/kg/min (mean +/- SD), which is less than in previous studies. When comparing HCPB and NCPB groups, elimination half-life (T1/2), TBC, volume of distribution (VD), area under the curve (AUC), and mean residence time (MRT) were similar. When comparing VASC and CPB patients, TBC and VD were greater in CPB patients than in VASC patients; thus, T1/2 (equal to 0.693 x VD/TBC) was similar. AUC was smaller in CPB patients because of hemodilution, but MRT was similar. It is concluded that ME clearance is lower in patients undergoing major vascular surgery than in healthy patients. The temperature and the duration of CPB do not seem to substantially influence the pharmacokinetics of ME when a bolus is administered. Parameters such as AUC, TBC, and VD appear modified by hemodilution during CPB; however, T1/2 and MRT, which allow comparisons between CPB and non-CPB patients, were similar in these patients.

Blood Proteins↗
PubMed1993

[Plasma concentrations of diltiazem and its metabolites in coronary surgery: relation with preoperative treatment].

Preoperative oral administration of calcium channel blocking agents has been found ineffective to prevent perioperative myocardial ischaemia. Our hypothesis was that low plasma concentrations may account for this inefficiency. Twenty-three male patients, scheduled for surgical myocardial revascularisation, were administered their usual anti-anginal treatment, including 180 to 360 mg of diltiazem since more than one week. The usual dosage was given at 8.00 p.m. on the day before surgery. On the morning of surgery, after withdrawal of a first blood sample, 60 mg of diltiazem were administered per month before the induction of anaesthesia. The anaesthesia was obtained with fentanyl, midazolam or flunitrazepam, pancuronium and isoflurane as required. The cardiopulmonary bypass (CPB) was associated with total haemodilution with Ringer's Lactate and a membrane oxygenator. A second blood sample was withdrawn after CPB. Plasma concentrations of diltiazem and its two active metabolites, N-monodemethyldiltiazem (MA) and desacetyldiltiazem (M1), were assessed by HPLC. Plasma diltiazem concentrations decreased from 78 +/- 66 (mean +/- SD) to 51 +/- 42 micrograms.l-1 (p < 0.05) with wide individual variations. These concentrations were under therapeutic levels in 18 out of 23 patients before (p < 0.05) with wide individual variations. These concentrations were under therapeutic levels in 18 out of 23 patients before induction and in 22 patients after CPB. The metabolite/diltiazem ratios remained constant. A dosage-plasma concentration relationship was observed preoperatively with diltiazem and MA. It is concluded that plasma concentrations of diltiazem should be optimized preoperatively in order to prevent myocardial ischaemia.

Aged↗
PubMed1993

Pharmacokinetics of ganciclovir in heart transplant patients undergoing continuous venovenous hemodialysis.

The pharmacokinetics of ganciclovir in patients with severe renal dysfunction is poorly defined. In this paper, we report the pharmacokinetics of ganciclovir in three anuric heart transplant patients under continuous venovenous hemodialysis (CVVHD). Ganciclovir was administered at a dose of 5 mg/kg every 48 h for at least 9 days. Samples from the arterial and venous blood lines and from ultrafiltrate were collected to calculate pharmacokinetic parameters, clearance of ultrafiltration, and sieving coefficient. Ganciclovir concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters (mean +/- SD) were the following: t1/2 beta 18.9 +/- 2.2 h, Cl 0.42 +/- 0.08 ml/min/kg, Vdss 0.68 +/- 0.10 L/kg. At the steady state the clearance of ultrafiltration was 12.9 +/- 1.9 ml/min (or 130 L/week) and the sieving coefficient was 0.84 +/- 0.08 with an average fraction of 89.7 +/- 10.6% of the administered dose removed by CVVHD. These results show that CVVHD is highly effective in removing ganciclovir from plasma. Furthermore, CVVHD appears more effective than intermittent hemodialysis. These data should be taken into account to optimize dosage adjustment of ganciclovir in patients under CVVHD, and until guidelines are available, careful monitoring of drug concentrations is recommended.

Adult↗
PubMed1993

[Problems posed by calcium antagonists and anesthesia: pharmacology, interactions, indications].

Calcium-channel inhibitors are widely used in therapeutics. Many patients administered calcium channel inhibitors undergo surgical procedures and the cardiologists or the anaesthesiologists are concerned with pharmacological interactions with anaesthetic agents such as halogenated gases. The combination of calcium channel inhibitors and halogenated anaesthetics may exert an additive effect on myocardial depression, conduction disturbances and arterial vasodilatation. The continuation of oral calcium channel inhibitors until the day of surgery is recommended provided the use of enflurane is restrained. Calcium-channel inhibitors such as dihydropyridines are currently administered intravenously to control intra and postoperative arterial hypertension while verapamil and diltiazem are used to treat supraventricular arrhythmias and myocardial ischaemic episodes. In patients with cardiac disease, haemodynamic monitoring may allow to anticipate or to treat episodes of cardiac dysfunction associated with I.V. calcium-channel inhibitors during the perioperative period.

Anesthetics↗
PubMed1992

Stability of diltiazem and its metabolites in human blood samples.

The stability of diltiazem and its metabolites in blood samples from patients under chronic diltiazem therapy was investigated. When whole blood was kept for 1 h at room temperature between sampling and centrifugation, the concentration of N-demethyldiltiazem (MA) decreased significantly, with an average loss of 24%. Under the same conditions, an average loss of 14% of diltiazem occurred, whereas the concentrations of the metabolites deacetyldiltiazem and N-demethyldeacetyldiltiazem did not change significantly. No significant decrease in MA and diltiazem concentrations was observed when whole blood was stored for 1 h in an ice bath. In spiked plasma samples kept at room temperature, only MA was unstable, with an average loss of 13% after 4 h. The present study shows the importance of observing rigorous conditions for the transport and treatment of blood samples. To achieve accurate determination of diltiazem and related compounds, the blood must be centrifuged immediately after collection or kept on ice for up to 1 h. The plasma samples must be immediately frozen at -80 degrees C and can be stored for up to 5 weeks before analysis. Using these rigorous conditions, we observed that MA is the main metabolite of diltiazem in plasma from patients under chronic oral diltiazem therapy.

Blood Preservation↗
PubMed1991

Modified high-performance liquid chromatographic method for the determination of ganciclovir in plasma from patients with severe renal impairment.

Using the rapid and sensitive high-performance liquid chromatographic (HPLC) method previously described for the analysis of ganciclovir in plasma, we have observed an interfering peak which co-elutes with the peak of ganciclovir in plasma samples from heart-transplant patients with severe renal insufficiency. A slight modification of this method allows the separation of the two peaks. The modified HPLC method, presented in this paper, is suitable for the accurate determination of ganciclovir in plasma from patients with severe renal impairment.

Chromatography, High Pressure Liquid↗
PubMed1991

High-performance liquid chromatographic determination of ganciclovir in plasma.

A rapid, selective and sensitive isocratic reversed-phase high-performance liquid chromatographic method for the determination of ganciclovir in plasma samples was developed. This method, which was applied to the analysis of plasma ganciclovir from heart transplant patients under ganciclovir therapy for cytomegalovirus infections, represents a suitable analytical tool for drug monitoring and pharmacokinetic investigations.

Chromatography, High Pressure Liquid↗
PubMed1991

Pharmacokinetics of methohexital during cardiovascular surgery with cardiopulmonary bypass.

The pharmacokinetics of methohexital after intravenous bolus administration was studied during cardiovascular surgery with cardiopulmonary bypass. The effect of body temperature (normothermia and hypothermia) during cardiopulmonary bypass on methohexital pharmacokinetics was investigated. The pharmacokinetic data obtained were compared with those from vascular surgery without cardiopulmonary bypass. A marked decrease in plasma methohexital concentrations and therefore in area under curve and a significant increase in clearance and in volume of distribution were observed in the cardiopulmonary bypass groups compared to the vascular surgery group without cardiopulmonary bypass. However, the elimination half-life and the mean residence time were similar in the 2 groups. Furthermore, the study shows that body temperature during cardiopulmonary bypass does not influence methohexital pharmacokinetics.

Adult↗
PubMed1990

Diagnosis of alcaptonuria: rapid analysis of homogentisic acid by HPLC.

The clinical and biochemical features of five cases of alcaptonuria were reported. The concentration of homogentisic acid was determined in urine and also in plasma using a rapid, sensitive and specific HPLC method. In all five cases, the concentrations of homogentisic acid were elevated in urine rising up to 46.5 mmol/24 h. In plasma, homogentisic acid levels ranged from 33 to 38 mumols/l. In healthy individuals, homogentisic acid was not detectable in plasma and urine. The method described represents a very useful and suitable analytical tool for the diagnosis of alcaptonuria.

Adult↗