Biomedical subjects

R Farinotti

Publications and source records attributed to R Farinotti.

At least 109 records · Page 6Linked to original sources

PubMed1993

Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide. A clinical and pharmacokinetic study.

BACKGROUND: The pharmacokinetic and pharmacodynamic properties of propofol indicate that this may be an appropriate agent for induction and maintenance of anesthesia in obese patients. This study was designed to assess the rates of recovery and the pharmacokinetics of propofol infusions in morbidly obese patients. METHODS: Anesthesia was induced and maintained using a stepwise infusion regimen of propofol in eight morbidly obese patients. The patients' lungs were ventilated with nitrous oxide:oxygen (66:34%). Pharmacokinetic parameters were calculated from iterative blood sampling during the propofol infusion and during 8 h after its completion. RESULTS: Results were compared with those from a concurrent study of propofol pharmacokinetics in nonobese adults. The initial volume of distribution of propofol was not modified in obese patients. Total body clearance increase was correlated to body weight (R = 0.76, 25.4 +/- 6.5 ml.kg-1.min-1, mean +/- SD). Volume of distribution at steady state was also correlated to body weight (R = 0.61, 1.63 +/- 0.54 l.kg-1, mean +/- SD). Propofol concentration at the time of eye opening in response to verbal command was 0.94 +/- 0.26 mg.l-1. CONCLUSIONS: Results from this study confirm the absence of propofol accumulation in morbidly obese patients when the current dosing scheme is used. Dosing schemes expressed in mg.kg-1 are the same as those in normal patients.

Adult↗

PubMed1993

Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients.

Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.

Aged↗

PubMed1993

Chronic alcoholism increases the induction dose of propofol in humans.

The doses of propofol that produce loss of consciousness were investigated in 26 patients with chronic alcoholism and in 20 patients with a history of small alcoholic intake undergoing ear, nose, and throat surgery under general anesthesia. Last ethanol consumption by the alcoholics was 24 h preoperatively, as they had no access to alcohol when admitted to the hospital. Propofol was infused at a rate of 1200 mL/h (200 mg/min). The doses required to produce (a) loss of verbal contact and (b) loss of ability to grasp a 20-mL syringe filled with water were recorded. At this time a 2-mL venous blood sample was collected to detect propofol blood concentrations. A painful stimulus was applied to the abdomen, and a positive or negative response was noted. The mean +/- SD dose of propofol required for loss of verbal contact was 2.7 +/- 0.42 mg/kg in the alcoholic group and 2.2 +/- 0.43 mg/kg in the control group (P < 0.001). The dose of propofol required for dropping the syringe was significantly higher in the alcoholic group, 4.2 +/- 1.02 mg/kg versus 3.2 +/- 0.75 mg/kg in the control group (P < 0.01). The two groups did not differ significantly regarding the propofol blood concentrations at loss of consciousness, or the frequency of response or no response to painful stimulus. These findings suggest that the doses of propofol required to induce anesthesia in chronic alcoholic patients are more than in patients who drink socially.

Adult↗

PubMed1993

[Luminescence and detection in liquid chromatography. II--Energy transfer from a stimulated molecule: indirect potentialization or sensitized luminescence].

Under the words of sensitized luminescence, the processes who include the transfers of energy from a donor to an acceptor are described. They are to the origin of new possibilities of detection in liquid chromatography by emission or inhibition of phosphorescence and fluorescence. These news technologies are illustrated by examples in pharmaceutic, biologic or food applications.

Chromatography, Liquid↗

PubMed1993

[Luminescence and detection in liquid chromatography. I: Change of environment of analytes].

The emissions of light by biorganisms or these obtained by alchemists were known since long time ago but the are used in analytical chemistry only when STOKES discovered that the intensity of this light was proportional to the quantity of the matter. The very large sensibilities reached, associated with the great separation's ability of the liquid chromatography allows to develop new processes for quantification of very low concentrations of luminescent or no luminescent molecules. Many pharmaceutical, biological toxicological environmental or alimentary applications show that it is possible in liquid chromatography to obtain a detection limit about the pico or femtomole when simple chemical process are used: direct potentialization of luminescence by addition of modifiers of the chemical environment of the analytes: solvents, cyclodextrins, surfactants, metallic ions, indirect potentialization of the luminescence by transfer of energy from an excited molecule: sensitized fluorescence and phosphorescence, excitation of the molecule by a chemical reaction or chemiluminescence. These aspects are emphasized and illustrated by some examples in three articles.

Chromatography, Liquid↗

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↗