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Biomedical subjects

R Farinotti

Publications and source records attributed to R Farinotti.

At least 145 records · Page 8Linked to original sources
PubMed1989

[Bone diffusion of cefotiam in men].

A 2g single dose of cefotiam was given by rapid intravenous injection to 17 patients undergoing total hip replacement as a prophylaxis. The concentrations of the antibiotic in plasma and femoral head (cancellous bone, cortical bone and capsule) were measured at different time (40 to 250 minutes) following the injection of the drug. Evaluation was done by liquid chromatography. Mean antibiotic concentrations were 70.5 micrograms/ml, 41.4 micrograms/g, 16.9 micrograms/g and 8.1 micrograms/g respectively in plasma, capsule, cancellous and cortical bones. 240 minutes following the injection, mean concentrations of cefotiam were higher than 2.3 micrograms/ml in plasma and 1.8 micrograms/g in bone. Diffusion in cancellous bone is twofold high as in cortical bone and elimination half lif is higher in bone than in plasma (248.8 minutes versus 59.6 minutes in plasma). These results suggest that a 2g intravenous bolus injection of cefotiam given at the induction of anaesthesia should provide an effective prophylaxis during total hip replacement.

Absorption↗
PubMed1988

Midazolam infusion for basal sedation in intensive care: absence of accumulation.

This study was designed to: (1) determine plasma midazolam concentrations producing adequate sedation in ICU patients; (2) establish an intravenous regimen to provide continuous sedation and rapid recovery after discontinuation of infusion. Initially, 13 ICU patients were given midazolam as a bolus injection, 0.20 mg.kg-1 over 30 s in order to define the midazolam plasma concentration corresponding to an adequate level of sedation. The optimal level was reached in a mean time of 61 +/- 26 min and the mean corresponding midazolam plasma concentration was 163 +/- 62 ng.ml-1. Estimations of the main pharmacokinetic parameters (elimination half life: 230 +/- 102 min, total body clearance: 520 +/- 283 ml.min-1, total volume of distribution: 2.23 +/- 1.15 l.kg-1) showed no marked differences with normal patients. From those variables, an infusion regimen (loading dose and maintenance rate) to provide long term (24 to 80 h) sedation was derived in 9 patients. The mean loading dose was 0.33 +/- 0.18 mg.kg-1 over 30 min and the mean continuous infusion dose was 0.06 +/- 0.02 mg.kg-1.h-1. The mean midazolam plasma concentration during infusion was 215 +/- 61 ng.ml-1, and the mean midazolam plasma concentration at the end of infusion was 199 +/- 93 ng.ml-1. The level of sedation was considered as optimal in most patients throughout the study. After discontinuation of infusion, the mean time for normalization of the mental state was 97 min.

Adult↗
PubMed1988

Pharmacokinetics of midazolam in anaesthetized cirrhotic patients.

The pharmacokinetics of midazolam were compared in cirrhotic patients (n = 10) and control patients (n = 9), during general anaesthesia. Total plasma clearance was 637 +/- 223 ml min-1 (mean +/- SD) in control patients and 402 +/- 170 ml min-1 in cirrhotic patients (P less than 0.05). The total volume of distribution was similar. Elimination half-life was 135 +/- 40 min in controls and 168 +/- 30 min in cirrhosis (P less than 0.05). Protein binding was evaluated by equilibrium dialysis in both groups at two concentrations of midazolam: 20 and 500 micrograms litre-1. No saturation occurred, but the free fraction was 4.9 +/- 1.7% in cirrhotic patients, compared with 1.9 +/- 0.6% in controls (P less than 0.01). Despite its mainly hepatic elimination, midazolam disposition appears to be only slightly impaired in cirrhotic patients.

Adult↗
PubMed1988

Pharmacokinetics and protein binding of propofol in patients with cirrhosis.

The pharmacokinetics and protein binding of propofol were studied in ten patients with cirrhosis and in ten control patients undergoing elective surgery. All patients received 2.5 mg.kg-1 propofol as an intravenous bolus injection for the induction of anesthesia. Whole blood propofol concentrations were measured at intervals up to 12 h, using a high-performance liquid chromatography (HPLC) technique. Propofol protein binding was estimated by equilibrium dialysis 10 min after injection of propofol. Individual propofol profiles for all patients were best described by a three-compartment open mammillary model. Rapid and slow propofol distribution half-times were observed, followed by an elimination phase with a half-time of 4-5 h. Propofol total body clearance was reduced (1.99 +/- 0.68 l.min-1) in the patients with cirrhosis but did not differ significantly from that in the control patients (2.30 +/- 0.61 l.min-1). The apparent volume of distribution at steady state (Vdss) was similar in the two groups. No significant difference in elimination half-life was observed between the two groups. Propofol was extensively bound (mean: 97-98%) to the plasma protein of both cirrhotic and control groups. This study shows that propofol pharmacokinetics and protein binding of propofol following a single intravenous bolus dose were not markedly affected by uncomplicated cirrhosis of the liver.

Adult↗
PubMed1988

Pharmacokinetics of propofol administered by continuous infusion in patients with cirrhosis. Preliminary results.

Anaesthesia was provided by an infusion of propofol in six healthy patients and six patients with hepatic cirrhosis. There were no significant differences between the groups with regard to the central compartment volume, distribution volume at steady state, total apparent distribution volume, total body clearance or elimination half-life, although the values were always greater in the cirrhotic patients. Recovery times were significantly longer in the patients with cirrhosis.

Anesthesia, Intravenous↗
PubMed1988

Pharmacokinetics of ofloxacin after single and multiple intravenous infusions in healthy subjects.

The pharmacokinetics of ofloxacin were investigated in eight healthy male volunteers. A single infusion (200 mg over 0.5 h) was performed on day 1, followed by a washout period of 2 weeks. Repeated administrations were performed for 4 days (200 mg every 12 h). Pharmacokinetic parameters were determined from the plasma decay curves of the single and the last of the multiple administrations. Ofloxacin kinetics after the single dose were best described by a two-phase curve with a total body clearance of 241.6 +/- 43.3 ml min-1, a volume of distribution of 112 +/- 23.1 liters, and an elimination half-life of 5.4 +/- 0.8 h. The extrapolated area under the curve (AUC0-infinity) was 14 +/- 2.3 mg.h liter-1. The pharmacokinetics were not significantly modified by repeated administration, demonstrated mainly by the AUC0-12 value of the last infusion (13.4 +/- 2.2 mg.h liter-1). We conclude that, with intravenous multiple doses every 12 h, the steady state is reached within 24 to 36 h and no abnormal accumulation or changes in pharmacokinetic parameters occur.

Adult↗
PubMed1988

Pyrazinamide and pyrazinoic acid pharmacokinetics in patients with chronic renal failure.

Pharmacokinetics of pyrazinamide and its major metabolite, pyrazinoic acid, were assessed in 10 chronic uremic patients treated by maintenance hemodialysis in comparison with 10 normal subjects. All subjects ingested a single dose of 1 g of pyrazinamide, the patients receiving the drug immediately after the end of a dialysis session. Bioavailability of pyrazinamide was only slightly increased in patients, its dialysis extraction coefficient being 55.3%. In contrast, pyrazinoic acid has an elimination rate-dependent metabolism with a bioavailability markedly increased in patients and a dialysis extraction coefficient of 59.8%. These data may lead to recommendations of a reduction in the dosage of pyrazinamide in dialysis patients. However, administering the usual dosage of the drug at the end of each dialysis session seems preferable to the daily administration of a reduced dosage.

Adult↗
PubMed1988

Left ventricular function during propofol and fentanyl anesthesia in patients with coronary artery disease: assessment with a radionuclide approach.

Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol alone and in combination with fentanyl on left ventricular (LV) volumes and function were investigated in 10 ASA III, unpremedicated patients (51-75 years) with coronary artery disease (NYHA II-III). Anesthesia was induced with propofol (2 mg/kg) followed by an infusion (100 micrograms.kg-1.min-1). Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled via a face mask (FECO2, 4-5%). Data acquisitions were serially obtained over 15 minutes after the bolus IV injection of propofol and 5 minutes after the injection of fentanyl (5 micrograms/kg). Propofol induced a rapid decrease (15%) in mean arterial pressure (MAP) exclusively related to a decrease in cardiac index (CI), without reduction in indexed systemic vascular resistances (SVRI). Despite the decrease in MAP, heart rate did not change. The decrease in CI was associated with a lower preload. After the addition of fentanyl, MAP decreased significantly (35%) below the last set of propofol measurements. The decrease in MAP was associated with a reduction in CI and SVRI. Fentanyl was also associated with a significant decrease in heart rate (16%) resulting in a decrease in CI, whereas stroke index and end diastolic volume did not change. Neither global ejection fraction (EF) nor end systolic volume changed significantly at any time, nor were there changes in the ECG or in regional ejection fractions (REF). The absence of changes in REF was consistent with lack of wall motion abnormalities of the left ventricle. Propofol alone and in combination with fentanyl does not alter LV performance in patients with good LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Characterization and quantification of PAF-acether (platelet-activating factor) as a heptafluorobutyrate derivative of 1-O-alkyl-2-acetyl-sn-glycerol by capillary column gas chromatography with electron-capture detection.

A gas chromatographic method with a glass capillary column and electron-capture detection is proposed for the characterization and quantification of 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF C16) using the corresponding 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-heptafluorobutyrate derivative and, as an internal standard, 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine. The reproducibility was approximately 5% and amounts as low as 20 pg could be measured. The method was specific and allowed the quantification of PAF C16 in supernatants from stimulated human polymorphonuclear neutrophils.

Chromatography, Gas↗
PubMed1987

[Effects of flunitrazepam on the baroreflex control of heart rate and on adrenergic activity].

The effects of intravenous flunitrazepam (25 micrograms . kg-1) on the baroreflex control of heart rate and plasma catecholamine levels were determined in ten ASA 1 unpremedicated patients. Plasma concentrations of flunitrazepam were also measured. The data was obtained before and 5, 10 and 15 min after flunitrazepam administration. The baroreflex gain was significantly decreased at 5 min, the time of the highest flunitrazepam plasma concentration. Catecholamine plasma levels were decreased at each study time. It was concluded that flunitrazepam induced a transient depression in baroreflex function and a sustained decrease in adrenergic activity.

Adult↗
PubMed1987

Morphine pharmacokinetics in renal failure.

The effect of chronic renal failure (RF) on the pharmacokinetics of morphine was studied in nine patients with end-stage RF, aged 58 +/- 8 yr (SD), and in seven control patients, aged 58 +/- 15 yr, undergoing peripheral surgery under general anesthesia. All patients received 0.2 mg X kg-1 as an intravenous bolus injection. Blood samples were collected over a 36 h period, and plasma concentrations were measured using a specific radioimmunoassay method. Unchanged morphine could be identified for only 12 h in all patients. The mean plasma concentrations of unchanged morphine were similar in the two groups, except in the first sample (5 min) where it was higher (P less than 0.05) in RF group. Patients with RF had a significantly smaller (P less than 0.05) central compartment (0.3 +/- 0.2 l X kg-1 versus 0.8 +/- 0.4 l X kg-1) than in the controls. Volume of distribution at steady state was also significantly (P less than 0.05) decreased in RF patients (2.8 +/- 1.0 l X kg-1) versus 3.7 +/- 1.2 l X kg-1 in the normal patients. The total apparent volume of distribution, the elimination half-life, and the plasma clearance were similar in the two groups. Identical peak levels of morphine metabolites were observed in the two groups, but plasma concentration of morphine metabolites was undetectable after 12 h in the control group and remained at a high level of 82 +/- 49 ng X ml-1 at 24 h and 83 +/- 57 ng X ml-1 at 36 h in RF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1987

Pentamidine aerosol in prophylaxis and treatment of murine Pneumocystis carinii pneumonia.

The efficacy and tolerance of pentamidine aerosol were evaluated in the prophylaxis and therapy of murine Pneumocystis carinii pneumonia. P. carinii pneumonia was induced in rats by corticosteroid immunosuppression. Pentamidine was administered three times weekly via a Bird micronebulizer. The actual amount of pentamidine inhaled was estimated by monitoring the ventilation of the rats during the aerosol administration. Pentamidine levels in blood, lung, liver and kidney samples were determined by high-pressure liquid chromatography after completion of the treatment. Efficacy was evaluated by examination of lung imprints. In the prophylactic treatment, 4.8- and 8.6-mg/kg doses of aerosolized pentamidine administered three times weekly for 7 weeks were effective in preventing P. carinii pneumonia in 80 and 100% of the rats, respectively. In the therapeutic studies, a 14.6-mg/kg dose of aerosolized pentamidine administered three times weekly for 3 weeks was effective both in curing the pneumonia and in clearing P. carinii cysts in 70% of the rats. In the remaining animals, although the pneumonia was cured, the cysts persisted. A dose-dependent effect of the drug was demonstrated in both prophylactic and therapeutic treatments. High lung/kidney and lung/liver ratios of pentamidine levels were demonstrated and were associated with good clinical, biological, and histologic tolerance.

Aerosols↗
PubMed1987

Pharmacokinetics of midazolam used as an intravenous induction agent for patients over 80 years of age.

The pharmacokinetic profile of 0.2 mg kg-1 midazolam given i.v., for induction of anaesthesia, was compared in young subjects and in those who were over 80 years of age. Thirty-five patients were allocated into four groups according to their sex and age. Plasma samples were drawn before midazolam injection and at regular intervals over 24 h following injection. Plasma midazolam concentrations were measured by electron capture gas-liquid chromatography. Equilibrium dialysis was used to assess the plasma protein binding of midazolam. Distribution volume (Vdss) was significantly increased in elderly subjects when compared to young subjects of the same sex (young vs. elderly males, Vdss = 1.22 +/- 0.31 l kg-1 and 2.47 +/- 0.98 l kg-1 respectively; and young vs. elderly females, Vdss = 0.91 +/- 0.29 l kg-1 and 1.70 +/- 0.78 l kg-1 respectively). Total body clearance was significantly reduced in elderly males compared with young males (5.60 +/- 1.77 ml min-1 kg-1 vs. 8.10 +/- 3.58 ml min-1 kg-1). No significant difference in clearance was found between young and elderly females (6.08 +/- 2.04 ml min-1 kg-1 vs. 9.14 +/- 3.36 ml min-1 kg-1). As a consequence, elimination half-life (T1/2E) was significantly prolonged in elderly compared to young males (8.52 +/- 5.4 h vs. 2.77 +/- 0.80 h). In contrast, T1/2E was unchanged in elderly compared to young females (2.99 +/- 0.86 h vs. 2.86 +/- 1.04 h). Midazolam plasma protein binding was not influenced by age and sex.

Adult↗