Biomedical subjects

R Farinotti

Publications and source records attributed to R Farinotti.

At least 19 recordsLinked to original sources

PubMed1992

Adaptive computer program for determination of absorption profiles by numerical deconvolution: application to amoxicillin absorption.

We have developed a specific numerical deconvolution program for the Apple Macintosh microcomputer. After comparison with other methods, we used the program to evaluate the influence of nifedipine on the absorption and bioavailability of amoxicillin. The technique provided a model-independent approach. This study shows that the simultaneous administration of nifedipine with amoxicillin leads to a significant increase in both the total quantity of amoxicillin absorbed (+22%) and the rate of absorption. Parameters of clearance, volume of distribution, and elimination were unaffected. Numerical deconvolution analysis showed that nifedipine did not modify the absorption kinetics of amoxicillin, which are characterized by a lag time followed by a constant rate of absorption, suggesting zero-order kinetics with first-order kinetics at the end of the process. The results suggest the existence of a specialized, saturable transport molecule for this antibiotic.

Adult↗

PubMed1992

Extrahepatic metabolism of propofol in man during the anhepatic phase of orthotopic liver transplantation.

We have investigated extrahepatic metabolism of propofol in 10 patients undergoing orthotopic liver transplantation (group 1) (mean age 38 yr, mean weight 60 (SD 7) kg) and compared it with that in 10 patients without liver dysfunction undergoing extrahepatic abdominal surgery (group 2) (mean age 56 yr, mean weight 68 (11) kg). A single i.v. bolus dose of propofol 0.5 mg kg-1 was injected into a peripheral vein 5 min after the beginning of the anhepatic phase in group 1 and 60 min after the induction of anaesthesia in group 2. Arterial blood samples were obtained at 5, 10, 15, 20, 30, 40, 50 and 60 min after injection and urine samples were collected every 15 min. Propofol concentrations in whole blood and urine were measured by high performance liquid chromatography with fluorescence detection. Propofol glucuronide was measured in urine by incubation with a specific beta-glucuronidase. The area under the time-blood concentration curve from 0 to 60 min was found to be significantly greater in group 1 (13743 (2830) micrograms litre-1 h-1) than in group 2 (7992 (4895) micrograms litre-1 h-1) (P less than 0.05). Unchanged propofol was not detected in the urine of either group. No significant difference was found in the amount of propofol glucuronide excreted by patients in group 1 (457 (269) micrograms) and in group 2 (921 (672) micrograms). The presence of a propofol metabolite in urine when the liver was excluded from the circulation suggests that extrahepatic metabolism occurred.

Adult↗

PubMed1992

In vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline against Plasmodium falciparum.

The in vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline was compared against chloroquine-resistant and -susceptible strains of Plasmodium falciparum using a semi-micro drug susceptibility test. For each strain, the corresponding enantiomers exhibited similar activities. The enantiomers of halofantrine were the most active against both susceptible and resistant strains, followed by the enantiomers of mefloquine and enpiroline.

Animals↗

PubMed1992

Modification of cefixime bioavailability by nifedipine in humans: involvement of the dipeptide carrier system.

We studied the action of nifedipine on the bioavailability of cefixime, a molecule absorbed via the gut wall dipeptide carrier system in the rat, and on the bioavailability of D-xylose, which is absorbed via a pH (and Na(+)-)-dependent transporter. Each compound was administered alone or in combination with 20 mg of nifedipine to eight healthy male volunteers. Nifedipine significantly increased the absorption rate of cefixime (20.7 +/- 4.3 versus 16 +/- 3.5 mg/h in the absence of nifedipine). The absolute bioavailability of cefixime alone was 31% +/- 6% compared with 53% +/- 1% (P < 0.01) in the presence of nifedipine. The observed peak concentrations in serum were significantly different (2.5 +/- 0.3 mg/liter without nifedipine and 3.7 +/- 1.1 mg/liter with nifedipine; P < 0.02). In contrast, nifedipine induced no significant differences in the pharmacokinetic profile of xylose following oral administration. We conclude that (i) cefixime is absorbed in humans by an apparently active process which can be enhanced by a calcium channel blocker, in this case, nifedipine; and (ii) nifedipine does not modify the activity of the pentose transporter.

Administration, Oral↗

PubMed1992

Penetration of vancomycin in uninfected sternal bone.

Concentrations of vancomycin in sternal bones of 10 patients undergoing cardiac surgery were studied at steady state, 48 h after starting intravenous prophylaxis. A sample of sternal bone was taken before (group I) or after (group II) cardiopulmonary bypass. The mean vancomycin concentrations in sternal bones were not significantly different between the groups and were 9.3 +/- 3.0 micrograms/g. The concentrations of vancomycin in sternal bones were always above the MICs for staphylococci, streptococci, and enterococci.

Adult↗

PubMed1992

Influence of Pneumocystis carinii pneumonia on serum and tissue concentrations of pentamidine administered to rats by tracheal injections.

Pentamidine isethionate was administered by the tracheal route to control rats and immunodepressed rats with Pneumocystis carinii pneumonia (PCP). The serum concentration of pentamidine base 20 min after the administration was higher in the PCP rats (309 +/- 165 ng/ml) than in the control animals (71 +/- 36 mg/ml; p less than 0.001); 90 min after the injection the proportion of the pentamidine administered was lower in the right lung of the PCP rats (29 +/- 15%) than in the control rats (57 +/- 23%; p = 0.038); the proportion of pentamidine in the left kidney was higher in the PCP rats (14 +/- 4%) than in the control animals (4 +/- 2%; p less than 0.001). Respiratory clearance of 99mTc-DTPA, an index of the permeability of the respiratory epithelium, was higher in the PCP rats (1.84 +/- 0.42 %/min) than in the controls (0.44 +/- 0.11 %/min; p less than 0.001). We conclude that the more rapid diffusion of pentamidine from the alveolar lumen to the pulmonary circulation is explained by the increased alveolocapillary permeability as a result of pneumocystosis.

Analysis of Variance↗

PubMed1992

[Evolution of the blood levels of propofol administered by continuous perfusion during extracorporeal circulation].

The pharmacokinetics of propofol administered in continuous infusion was studied in 10 patients without left ventricular insufficiency during extracorporeal circulation (ECC) with hemodilution, for aortocoronary bypass. After a dosage of 1.5 mg.kg-1 during anaesthetic induction, the blood level was 4,800 micrograms.l-1. Under continuous infusion levels remained very high: they decreased by 40% during EEC induction and rose more than 10% when artificial ventilation started again. These modifications can be explained by physiological variations induced by EEC (non pulsated flow, redistribution, vasoconstriction, hemodilution, hypothermia) and they lead to adapt dosages in this type of anaesthesia.

Aged↗

PubMed1992

Efficacy of continuous zidovudine infusion at early stages of retroviral infection in mice.

We studied the pharmacokinetics of zidovudine (ZDV) in mice after twice-daily s.c. bolus injections and during continuous infusion with s.c. ALZET mini-osmotic pumps. We also compared the antiretroviral efficacy of these two modes of administration against Friend leukemia virus (FLV) infection. Mice were infected by retro-orbital inoculation of about 50 focus-forming units (ffu) of FLV, and treatment was started 1 or 4 h later with ZDV at 40 mg/kg/day for 5 days. Efficacy was evaluated in terms of spleen weight and/or virus titer (spleen focus assay) on day 21 in comparison with untreated infected mice. In a separate experiment, survival time after infection was also monitored over a 140-day period. Plasma concentrations of ZDV were determined by means of high-performance liquid chromatography. Following bolus administration, the peak plasma ZDV concentration (30.5 mg/ml) was reached within 10 min, and elimination was rapid (mean half-life, 0.7 h). During the continuous infusion, the mean concentration was constant at about 1.2 mg/ml. After 5 days of treatment, continuous ZDV infusion consistently inhibited virus-induced splenomegaly by more than 97%; bolus injections were less effective with inhibition ranging from 13 to 98%. These results suggest that moderate constant levels of ZDV have greater antiretroviral efficacy than intermittent high concentrations.

Animals↗

PubMed1992

[Pulmonary and bronchial kinetics of cefuroxime after a single 500 mg intramuscular injection].

Thirty-two patients (28 males; mean age 56 +/- 10 years) who were undergoing bronchopulmonary exeresis surgery were included in this study of the pulmonary (pulm), bronchial (br), and plasma (pl) kinetics of cefuroxime after a single 500 mg intramuscular injection. Twenty-nine bronchial specimens and 38 pulmonary and plasma specimens were taken on average at the following times after the cefuroxime injection: 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h. Cefuroxime was assayed using HPLC on ground tissues, with a correction for contamination by blood. Peak concentrations (C) were found after one hour (Cpl = 11.6 +/- 0.8 micrograms/ml; Cpulm = 7.3 +/- 3.3 micrograms/g; Cbr = 3.7 +/- 1.5 micrograms/g) with the following residual values after 8 hours: Cpl = 0.94 +/- 1.04 micrograms/ml, Cpulm = 0.49 +/- 0.45 micrograms/g, Cbr = 0.15 +/- 0.07 micrograms/g (means +/- 1 SD). Elimination kinetics were monoexponential and similar in plasma, lung tissue and bronchial tissue (elimination half-lives: 1.74 h, 1.66 h, and 1.56 h, respectively), suggesting that all three elements belong to the same pharmacokinetic compartment. Mean intrapolated area-under-the-curve values (AUC) were 33.58 micrograms.ml-1.h (plasma), 20.08 micrograms.g-1.h (lung), and 10.22 micrograms/g-1.h (bronchus). The AUCpulm/AUCpl and AUCbr/AUCpl ratios were 0.60 and 0.30, respectively, in agreement with mean values of tissue level/simultaneous plasma level ratios (lung: 0.59; bronchus: 0.33).

Adult↗

PubMed1991

Determination of zopiclone enantiomers in plasma by liquid chromatography using a chiral cellulose carbamate column.

The enantiomers of zopiclone were determined in human plasma using a sequential achiral-chiral liquid chromatographic method. Zopiclone was separated from the biological matrix and quantified on an achiral silica column. The limit of detection was 5 ng/ml. The eluent fraction containing zopiclone was collected, evaporated, reconstituted with the mobile phase and injected onto a chiral cellulose carbamate column where the enantiomeric ratio was calculated. This validated method, applied to a pilot study, suggests that pharmacokinetics of zopiclone is stereoselective.

Azabicyclo Compounds↗

PubMed1991

[Pentamidine aerosol in the preventive treatment of pneumocystosis in AIDS patients. Comparison of two salts and two nebulizers].

In a randomized trial conducted in AIDS patients requiring prophylaxis against pneumocystosis we compared two pentamidine salts, isethionate (I) and mesylate (M), and two nebulizers (a modified ultrasonic Ultraneb 99 Devilbiss nebulizer, and a disposable jet nebulizer). Patients were randomized to one or the other nebulizer and received alternatively, once every other week, the two pentamidine salts in the IMIM or MIMI order. Characteristics and the side effects of the two courses of each pentamidine salt, as well as drug delivery by each nebulizer during the first course, were studied in 48 patients. The ultrasonic nebulizer was more effective (nebulization time: 19.8 +/- 7.3 mn versus 30.7 +/- 11 mn) and produced less side-effects (FEV1 decrease: 186 +/- 677 versus 571 +/- 708 ml) than the jet nebulizer. The mesylate salt tended to produce more side-effects than the isethionate, but the difference was not significant (FEV1 decreases: 439 +/- 688 ml and 295 +/- 756 ml respectively). We concluded that the best therapeutic procedure is to use pentamidine isethionate delivered by the ultrasonic nebulizer.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Effect of upper abdominal surgery and cirrhosis upon the pharmacokinetics of methohexital.

The pharmacokinetic profile of methohexital was studied in cirrhotic patients (n = 8), patients undergoing upper abdominal surgery (n = 8) and orthopaedic patients under general anaesthesia (n = 8). The total plasma clearance of methohexital was unchanged in cirrhotics: 54 +/- 22 l.h-1 (mean +/- s.d.) as well as in patients undergoing upper abdominal surgery: 60 +/- 14 l.h-1 in comparison to orthopaedic surgery: 70 +/- 24 l.h-1. The central volume and total volume of distribution and the distribution and elimination half-lives were similar between the three groups. Despite its hepatic dependent elimination, methohexital elimination kinetics were unchanged in patients undergoing upper abdominal surgery and in cirrhosis. Owing to the high hepatic extraction ratio of methohexital, its elimination should be influenced by the hepatic blood flow. The unchanged elimination kinetics presently observed in patients with cirrhosis or those undergoing upper abdominal surgery suggest that the hepatic blood flow is less diminished than expected in these patients.

Abdomen↗

PubMed1991

Type RI resistance to halofantrine in West Africa.

A case of recrudescent falciparum malaria after halofantrine treatment is described. The patient contracted Plasmodium falciparum in Ivory Coast and was treated with halofantrine. Plasma levels of halofantrine and its metabolite were adequate. Thirty-one days after treatment, the patient was rehospitalized with symptoms of malaria. Recrudescence was confirmed by microscopic examination, indicating a type RI resistance to halofantrine. Mefloquine was given to treat recrudescent malaria. The parasite was susceptible to chloroquine and quinine in vitro but displayed elevated values of 50% inhibitory concentration for mefloquine and halofantrine. The case reminds us that chloroquine still has an important therapeutic role against African strains of P. falciparum and that mefloquine and halofantrine should be reserved for multi drug-resistant P. falciparum.

Animals↗

PubMed1990

Determination of the enantiomers of mefloquine in plasma and whole blood using a coupled achiral-chiral high-performance liquid chromatographic system.

A coupled achiral-chiral high-performance liquid chromatographic system has been developed for the determination of the enantiomers of mefloquine, (+)-MFQ and (-)-MFQ, in plasma and whole blood. The MFQ was separated from the interfering components in the biological matrix and quantified on a cyano-bonded phase, and the enantiomeric composition was determined on an (S)-naphthylurea chiral stationary phase. The two columns were connected by a switching valve equipped with a silica precolumn. The precolumn was used to concentrate the MFQ in the eluent from the achiral column before backflushing onto the chiral phase. The coupled-column system was validated and applied to the analysis of a pilot study of the pharmacokinetics of (+)- and (-)-MFQ in plasma and whole blood.

Chromatography, High Pressure Liquid↗

PubMed1990

Comparison of serum hydroquinidine determination by fluorescence polarization immunoassay and liquid chromatography.

Hydroquinidine is a structural analogue of quinidine. It is used in the treatment and prevention of cardiac arrhythmias and necessitates serum monitoring. Fluorescence polarization immunoassay (FPIA) of quinidine has been proposed and we have tested the performance of this assay for hydroquinidine using its cross-reaction with quinidine. Tracer (quinidine labelled with fluorescein) and anti-serum were purchased from Abbott S.A. Standard curves were obtained using specifically prepared hydroquinidine calibrators and within-run and run-to-run precision values (expressed as relative standard deviation) (RSD) lower than 5.3% (n = 10). In order to evaluate specificity of this assay in the clinical situation, FPIA and liquid chromatography results were compared.

Chromatography, High Pressure Liquid↗

PubMed1990

Acebutolol and diacetolol plasma levels in patients undergoing myocardial revascularization with hypothermic cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) has been reported to alter the disposition of numerous drugs and consequently to modify their plasma levels. The present study was designed to delineate the time course of acebutolol (a cardioselective beta-blocker) and diacetolol (its main metabolite) plasma levels in seven patients undergoing myocardial revascularization with hypothermic CPB. All patients were given oral acebutolol twice daily until 3 hours before surgery. Initiation of CPB produced an immediate and significant, but transient, decrease in acebutolol and diacetolol plasma concentrations. Cessation of CPB was not associated with an increase in plasma beta-blocker levels. It is concluded that CPB does not induce major alterations in the time course of acebutolol and diacetolol plasma concentrations.

Acebutolol↗

PubMed1990

[Respiratory effects of almitrine on various levels of the fraction of inspired oxygen. A study in the anesthetized dog].

The effects of intravenous almitrine under normoxic, hyperoxic, and hypoxic conditions were studied in 5 male beagle dogs (mean weight 15.2 +/- 5 kg) anaesthetized with thiopentone. Plasma concentrations of thiopentone were maintained constant at 27-29 mg.1(-1). Each animal underwent twice the three different experiments, with a lapse of a fortnight between each experiment: a) breathing room air, with intravenous administration of 1 mg.kg-1 almitrine over 30 s, b) breathing room air, then pure oxygen for 15 min, followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing pure oxygen, and c) breathing room air, then progressively less oxygen (FIO2 0.18, 0.16, 0.14, 0.12 for 5 min each), followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing a mixture with 12% oxygen. Tidal volume, respiratory rate, minute ventilation, inspiratory and expiratory duration, arterial pH, PaO2 and PaCO2 were measured respectively in room air, after 100% oxygen, in hypoxia (FIO2 = 0.12), before, 5 and 10 min after the injection of almitrine. Hyperoxia depressed ventilation (-21%), whilst hypoxia stimulated it (+126%), although significantly less than in the awake animal. Almitrine restored the respiratory response to hypoxia, but hyperoxia did not suppress respiratory stimulation due to the drug. It would therefore seem likely that almitrine acts on peripheral arterial chemoreceptors, but also on other structures. The results of this study suggest that almitrine may be useful in restoring the respiratory response to hypoxia during recovery from anaesthesia.

Almitrine↗

PubMed1990

Pharmacokinetics of propofol infusions in patients with cirrhosis.

We have compared the pharmacokinetics of propofol as an infusion in 10 control and 10 patients with cirrhosis. Anaesthesia was induced within 3-4 min during administration of an infusion of propofol 21 mg kg-1 h-1. After 5 min, the infusion was decreased in a stepwise manner to 12 mg kg-1 h-1 and subsequently 6 mg kg-1 h-1. The mean recovery time after discontinuation of the infusion was significantly longer in the cirrhotic group; however, when patients opened their eyes, blood concentrations of propofol were similar in both groups (1 micrograms ml-1). Pharmacokinetic analysis was performed from the beginning of infusion to 8 h after termination. Total body clearance was not reduced significantly in cirrhotic (1.56 (SD 0.48) litre min-1) compared with control (1.75 (0.32) litre min-1) patients. The volume of distribution at steady state was significantly greater in patients with cirrhosis than in control patients (202 (82) litre vs 121 (49) litre). However, this difference did not change terminal elimination half-life. The pharmacokinetics of propofol given by infusion to maintain general anaesthesia were not affected markedly by moderate cirrhosis.

Adult↗