Quality of life, pain and return to normal activities following laparoscopic donor nephrectomy versus open mini-incision donor nephrectomy.

PURPOSE: We evaluated pain, convalescence and health related quality of life in patients undergoing laparoscopic and open mini-incision donor nephrectomy. MATERIALS AND METHODS: We compared the records of consecutive patients who underwent laparoscopic and mini-incision open donor nephrectomy from our donor nephrectomy data base in retrospective fashion using 2 questionnaires. The first questionnaire evaluated postoperative pain, return to functioning time and satisfaction. The second questionnaire was the RAND 36-Item Health Survey, version 2, a standardized and validated health survey quality of life assessment tool. Mean patient sex, age and followup were similar for the 2 groups. All data were analyzed using the 2-tailed t test for independent variables with commercially available statistical analysis software. RESULTS: Pain in the laparoscopic group was significantly less than in the mini-incision group at all followup time points (p <0.05). Statistically significant differences demonstrated that laparoscopy led to more rapid recovery time in certain categories, including walking, discontinuation of prescribed oral pain relievers, return to driving, and resumption of normal work and home daily activities. More subjective questions in the survey showed high levels of acceptance for the 2 procedures. Using the RAND 36-Item Health Survey, version 2 health related quality of life was significantly higher in the laparoscopy group in 3 domains that measure bodily pain, physical functioning and emotional role functioning. However, each group scored at or above age matched American averages in all domains. CONCLUSIONS: The laparoscopy group had significantly less postoperative pain and required less time to return to normal functional activities than the mini-incision group. In addition, the laparoscopic group showed significantly higher quality of life scores than the mini-incision group in 3 domains.

Pharmacokinetics of milnacipran in liver impairment.

The pharmacokinetics of single 50 mg oral and intravenous doses of milnacipran, a new non tricyclic antidepressant drug, were compared in 11 chronic liver impaired (LI) subjects and in 6 control subjects. Hepatic impairments, classified according to the PUGH scale were moderate (1 grade A), intermediate (6 grade B) and severe (4 grade C). Concentrations of unchanged drug and its conjugated form (its main metabolite) were measured in plasma and urines. In control subjects, milnacipran present high absolute bioavailability (mean value of 90%). Around 50% of the dose are excreted in urines as unchanged, while around 14% are excreted as glucuroconjugate. The remaining is composed of free and conjugated phase I inactive metabolites. Administration of milnacipran in LI subjects results in non significant changes in its pharmacokinetics, although its variability is increased. Unchanged drug exposure is not modified in LI subjects, while plasma levels of the conjugate are slightly decreased compared to the control group. This could either be due to a slight reduction in the conjugation process, or to a change in the distribution of the drug as urine excretion of both unchanged and conjugated forms are not modified compared to the control group. A few LI subjects present supra-bioavailability resulting in higher drug exposure after oral administration than after intravenous infusion. These modifications are not clinically relevant as drug exposure of the parent drug is not modified. As the unchanged drug is the only compound responsible for the activity of milnacipran, no dosage adjustment is needed in patients presenting liver impairment.

[Does glycemic level influence the pharmacokinetics of an antibiotic (cefoperazone)?]. / Existe-t-il une influence du niveau glycémique sur la pharmacocinétique d'un antibiotique (la céforpérazone)?

Hyperglycemia may modify pharmacokinetics of some antibiotics as shown in the literature. We studied the influence of glycaemic levels on pharmacokinetics properties of cefoperazone in 12 type 1 insulin dependent diabetic patients. Hyperglycaemia was obtained by a reduction of one quarter of their usual insulin dosage and normoglycaemia by an artificial pancreas (Biostator GCIIS). Cefoperazone had a high protein affinity and a high biliary elimination. Pharmacokinetic study was performed during a 8 hour period following one gram intravenous bolus. We did not found any influence of glycaemic level (normoglycaemia or hyperglycaemia) on the pharmacokinetic parameters of cefoperazone.

[Pharmacokinetics of chlormezanone in healthy volunteers]. / Pharmacocinétique de la chlormézanone chez le volontaire sain.

The kinetics of chlormezanone were determined after oral administration of single (400 mg) and multiple doses (400 mg/day during 8 days) in eight young healthy male subjects. Plasma levels determination had been carried out by HPLC. After single dose administration, Cmax concentrations 4.62 +/- 0.75 mg/l were obtained (Tmax) 2.18 +/- 1.49 h after drug intake. Area under plasma concentrations time curve was 224.93 +/- 27.79 mg.h/l and terminal half-life 40.50 +/- 4.19 h. On chronic regimen, chlormezanone accumulates in the body: trough plasma concentrations are significantly increased from Day 7 (2.97 +/- 0.45 mg/l) to Day 9 (5.41 +/- 0.90 mg/l) and reach the steady state faster than it can be expected from half-life (40 hours) and dosing interval (24 hours). Elimination is faster (T1/2 beta = 37.14 +/- 3.18 h) after chronic regimen. Area under curve during dosing interval at steady state (164.19 +/- 21.70 mg.h/l) is significantly lower than the area under curve between zero and infinity in the single dose sequence (224.93 +/- 27.79 mg.h/l). These results agree with probable induction effect of chlormezanone on its own metabolism.

The influence of the route of administration of imipramine on imipramine and desipramine blood levels.

Imipramine was used to treat 18 depressed inpatients for 22 days. Imipramine 2 mg/kg/day was administered from day 0 to day 14 intramuscularly, and 4 mg/kg/day was administered orally from days 15-21. Two pharmacokinetic studies were performed, the first at the end of the intramuscular phase (day 14) and the second at the end of the oral phase (day 21). Imipramine and desipramine blood levels were measured every hour from 8 a.m. to 4 p.m. Between these two pharmacokinetic evaluations, blood levels of imipramine and desipramine were measured every morning at 8 a.m. During intramuscular administration, the parent drug imipramine predominated in the plasma and, conversely, the desmethylated metabolite predominated during oral administration. With the changeover in route of administration, the doubling of the dose kept the blood levels of imipramine equal, while desipramine increased; the sum of imipramine and desipramine also increased, and the ratio of imipramine and desipramine decreased sharply, the median ratio changing over 3 days from 1.50 (day 15) to 0.62 (day 18).

Pharmacokinetics of a new macrolide, roxithromycin, in infants and children.

The pharmacokinetics of roxithromycin was investigated after oral administration of 2.5 mg/kg doses given 12 hours apart during 6 days in infants and children. These 18 subjects suffering from a respiratory tract infection were divided into three age groups: group I less than 18 months, group II less than 5 years, group III less than 13 years. At day 6, the elimination plasma half-life had an average value (mean +/- SD) of 19.8 +/- 9.7 h (group I), 21.0 +/- 9.4 h (group II) and 20.8 +/- 6.9 h (group III), respectively. The maximum concentration of roxithromycin (Cmax) was attained between 1 and 2 hours after dosing with mean values of 10.1 +/- 3.0 mg/l (group I), 8.7 +/- 4.9 mg/l (group II), 8.8 +/- 7.0 mg/l (group III). All the calculated pharmacokinetic parameters did not significantly differ from one group to another. The kinetics of roxithromycin in infants and children seemed to be age independent and showed no accumulation after repeated doses. During 12 hours, the plasma concentrations were above MIC of microorganisms generally present in respiratory tract infections. Two daily doses of 2.5 mg/kg of roxithromycin 12 hours apart may be proposed in infants and children.

Micro-method for the determination of roxithromycin in human plasma and urine by high-performance liquid chromatography using electrochemical detection.

A simple and sensitive high-performance liquid chromatographic micro-method for the determination of roxithromycin in human plasma and urine is described. A dichloromethane extract of the sample was chromatographed on a C18 reversed-phase column with acetonitrile-83 mM ammonium acetate-methanol (55:23:22, v/v) adjusted to pH 7.5 with acetic acid as the mobile phase. Roxithromycin and the internal standard, erythromycin, were detected by dual coulometric electrodes operated in the oxidative screen mode. The applied cell potential of the screen electrode was set at +0.7 V and the sample electrode at +0.9 V. The intra- and inter-assay coefficients of variation were less than or equal to 7.0%. The detection limit (signal-to-noise ratio = 3) was 0.1 microgram/ml for both plasma and urine. A study of drug stability during sample storage at 4, 20 and 37 degrees C showed no degradation of roxithromycin. The method is convenient for clinical monitoring and pharmacokinetic studies.

[Delayed-action theophylline versus placebo on the ventilatory function of stable asthmatic patients. Study in relation to circadian rhythm]. / Essai d'une théophylline longue action contre placebo sur la fonction ventilatoire de l'asthmatique stable. Etude en fonction du rythme nycthéméral.

The aim of this study was to measure the results of a long-acting theophylline (Planphylline) on the flow rates of stable asthmatic patients while taking into account the spontaneous circadian variations of the ventilatory function. 27 patients were involved in this randomized, double-blind, cross-over trial; they received 10 mg/kg/day in two doses at 8.30 a.m. and 8.30 p.m or the placebo. The product was administered over two 4-day periods separated by a 3-day wash-out period. The theophylline concentration and bronchial flows (FEV1; MMEFR 25-75) were measured at 8 a.m., 10.30 a.m., noon, and 3 p.m. on days 1 and 4 of each period; 11 patients measured their hourly PEFR from 8 a.m to 10 p.m those same days. The results can be analysed for 19 patients, including the 11 who measured their PEFR. The first day of treatment (D1), the theophylline concentration rose regularly without going above 10 micrograms/ml. On the fourth day of treatment (D4), the mean maximum concentration was above 10 micrograms/ml and the 8 a.m rate was superior to 8 micrograms/ml for 14 patients out of 19. The bronchodilating effect of Planphylline is significant for all bronchial flow rates (FEV1 less than 0.01; MMEFR 25-75 less than 0.05; PEFR less than 0.01, n = 11). On D1, the FEV1 becomes normal. On D4, the MMEFR 25-75 is still only partially improved, in spite of the theophylline concentration obtained. Because of the spontaneous diurnal improvement of bronchial rates, only the 8 a.m, 10.30 a.m. and 3 p.m. FEV1 obtained with Planphylline are statistically different from those obtained with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

[Influence of fever on cefotaxime pharmacokinetics]. / Influence de l'hyperthermie sur la pharmacocinétique du céfotaxime.

The role of fever on cefotaxime disposition was studied in ten hyperthermic patients. Each subject received intravenously 1 g of cefotaxime on two separated occasions, first when the body temperature was more than 39 degrees C then during a basal state (37 degrees C). Blood samples were taken over 12 hours and urine was collected for 24 hours after injection. After dosing cefotaxime and its metabolite by high performance liquid chromatography, the pharmacokinetic parameters were calculated, especially: plasma and renal clearance, volume of distribution at steady state, area under the curve, and elimination half-life. There is no significant difference in cefotaxime and desacetylcefotaxime disposition between these two states. Hyperthermia has no influence on pharmacokinetics of this cephalosporin.

Pharmacokinetics of rilmenidine in healthy subjects.

Rilmenidine is a novel alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once or twice daily. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability factor close to 1 and a maximal plasma concentration achieved within 2 hours. Rilmenidine was not subject to presystemic metabolism. Distribution was independent of the free fraction because rilmenidine was weakly bound to plasma proteins (less than 10%). The volume of distribution was approximately 5 l.kg-1 (315 liters). Elimination was rapid with a total body plasma clearance of approximately 450 ml.min-1 and an elimination half-life of approximately 8 hours. Renal excretion was the major elimination process (two-thirds of the total clearance). Metabolism was very poor, with a renal elimination of rilmenidine as the parent drug (urinary fraction of rilmenidine was about 65% and no metabolite plasma levels were detected). Linear pharmacokinetics were demonstrated for rilmenidine from 0.5 to 2 mg but, at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linear disposition of rilmenidine with dose was confirmed.

Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis.

Kinetics of fosfomycin were investigated in six patients undergoing continuous ambulatory peritoneal dialysis. Each subject received both an i.v. and an i.p. 1 g dose of fosfomycin with a one week washout between doses. Fosfomycin was assayed by a microbiological diffusion technique. After intravenous injection the fosfomycin serum kinetic parameters were as followed: elimination half-life (t1/2 beta) 38.4 +/- 8.7 h; volume of distribution 0.32 +/- 0.02 l/kg; total plasma clearance 7.0 +/- 1.4 ml/min and peritoneal clearance 3.2 +/- 0.2 ml/min. Dialyzate fosfomycin concentrations reached a maximum mean value of 32.2 +/- 2.8 micrograms/ml at 4 h post-injection and fosfomycin was detectable in dialyzate samples for up to 72 hours post-dosing. After intraperitoneal instillation, fosfomycin appeared in the serum rapidly and the mean peak plasma concentration was 36.2 +/- 2.8 micrograms/ml at the 4th h. The absorption rate (ka) was 0.580 +/- 0.039 h-1 and the absorption of fosfomycin from peritoneal space was 68.4 +/- 6.0%. These data suggest a bidirectional exchange through the peritoneal membrane. Intraperitoneal administration of 1 g either 48 h apart for anephric patients or 36 h apart for patients with residual renal function may achieve therapeutic serum concentrations.

Micromethod for determination of ceftriaxone in plasma and urine by high-performance liquid chromatography.

A sensitive and rapid high-performance liquid chromatographic method for the determination of ceftriaxone in human plasma and urine is described. A C18 reversed phase column is used; the mobile phase comprises water-methanol-triethylamine (750:250:4v/v/v) adjusted to pH 3 with orthophosphoric acid. Quantitation is performed at 270 nm with cefazolin as the internal standard. This method involves precipitation of proteins from fluids with acetonitrile followed by extraction of endogenous compounds with chloroform and injection of the upper aqueous phase on to the chromatograph. Relative standard deviations for between-day and within-day assays are 6.2%. The detection limit is 0.5 microg(-1) in plasma and urine. Studies of drug stability during sample storage, sample pretreatment and chromatography showed no degradation of ceftriaxone or of the internal standard. The method is convenient for clinical monitoring and for pharmacokinetic studies.

Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors.

Following oral administration in the fasting healthy subject, the mean maximum concentration of tianeptine is 334 +/- 79 ng/ml. Absorption of tianeptine from the tablet form is rapid and complete. Maximum plasma concentration is obtained by the first hour following administration (0.94 +/- 0.47 h). Absolute bioavailability is 99 +/- 29%. Tianeptine is thus rapidly and completely absorbed in the tablet form and is not subject to first-pass effect. Distribution of tianeptine in the body is characterized by the following: its rapidity, the mean distribution half-life being about 0.7 h; its limited extent, the apparent volume of distribution being about 0.8 L/kg (0.77 +/- 0.31 L/kg); and protein binding, which averages 93.8 +/- 2.4%. Elimination of tianeptine is characterized by a short mean half-life of 2 h 30 min (2.5 +/- 1.1 h) and by renal excretion of 0.4 ml/min (0.4 +/- 0.4 ml/min). Tianeptine is extensively metabolized. Major metabolites are analogs of tianeptine with a C5 and C3 lateral chain and a N-demethylated derivative. Studies have shown negligible influence on pharmacokinetic parameters of chronic alcoholism even in case of hepatic cirrhosis. In renal failure, and in the elderly, studies have revealed a 1-h prolongation of elimination half-life which suggests that the dosage should be limited to two tablets per day in such cases.

Pharmacokinetics of roxithromycin in paediatrics.

Macrolides are well known for their high lipid solubility and good tissue penetration. The pharmacokinetic properties of roxithromycin, a new semisynthetic macrolide, appear to be very interesting in healthy adult patients. Five paediatric pharmacokinetic studies are summarized and show that the pharmacokinetic properties of roxithromycin in paediatrics are very similar to those previously reported in adults and suggest that the same dose every 12 h is appropriate in paediatrics, 2.5 mg/kg. The diffusion of roxithromycin into upper respiratory tract tissues appears to be good in children.