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Biomedical subjects

A Arancibia

Publications and source records attributed to A Arancibia.

At least 19 recordsLinked to original sources
PubMed1998

Pharmacokinetics of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Exposure to high altitude results in significant physiologic changes and may precipitate mountain sickness, ranging from mild symptoms above 2,500 m to severe symptoms above 4,000 m. In a previous study, changes in the pharmacokinetics of meperidine were observed after exposure to high altitude. This study was conducted to investigate whether similar changes occur for acetazolamide, which is prescribed for prophylaxis of acute mountain sickness. Acetazolamide 250 mg was administered orally to young, healthy male volunteers in groups of 12 each: those residing at sea level (group L), these same volunteers on the day after arrival at high altitude (4,360 m, group HA), and volunteers living at high altitude for 10 months or longer (group HC). Serial blood samples were collected for 24 hours and acetazolamide concentrations were measured in whole blood, plasma, and plasma water. The elimination rate constant (lambda z) was significantly increased in group HA compared with group L. Clearance uncorrected for bioavailability (Cl/F) increased significantly in group HA compared with group L, and further increased in group HC. Apparent volume of distribution (Vz/F) was decreased by 17% in group HA compared with group L, and increased by 37% in group HC compared with group HA. Mean residence time (MRT) was significantly decreased in group HA compared with groups L and HC. Erythrocyte (RBC) uptake increased significantly after a significant increase in RBC count in group HC compared with group L. The extent of protein binding (EPB), however, was significantly decreased in group HA compared with groups L and HC. Free acetazolamide concentrations were significantly lower in group HC than in group L 12 hours after administration. Based on these observations, it is suggested that patients travelling to high altitude, especially altitudes above 4,000 m, should be closely monitored and acetazolamide dosage adjusted as necessary.

Acetazolamide↗
PubMed1998

Urinary excretion of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Acetazolamide is recommended for the prophylaxis of acute mountain sickness symptoms which sets in on climbing to high altitudes (H) above 2,500 m. It is primarily excreted unchanged in urine. In a previous study, we reported on the changes in urinary excretion of meperidine and its metabolite normeperidine on exposure to high altitude. In this study, we investigated the effect on urinary excretion of acetazolamide. The study was carried out in three groups of 12 healthy male volunteers each: at sea level (group L), these same volunteers the day after arrival at high altitude of 4,360 m (group HA), and subjects residing for approximately 10 months at high altitude (group HC). Urine was collected for the periods of 0-2, 2-4, 4-8, 8-12, 12-24 and 24-36 h after peroral administration of a single 250 mg dose. Urinary pH was measured and the concentrations of acetazolamide were determined. There were no significant changes observed in the amount of acetazolamide excreted in urine over 36 h. The urinary pH ranged from 4.5 to 7.8 for L, from 4.2 to 6.9 for HA and from 3.1 to 6.7 for HC. The Fel (fraction eliminated unchanged in urine) was calculated from the amount excreted in 36 h in urine and dose, assuming a bioavailability of 1 based on literature data. No significant changes in Fel were seen.

Acetazolamide↗
PubMed1996

Pharmacokinetics of meperidine in healthy volunteers after short- and long-term exposure to high altitude.

Increased numbers of erythrocytes have been shown ex vivo to increase meperidine uptake, and one of the major physiologic changes that occurs at high altitude is an increase in hematocrit and erythrocytes. A study was therefore conducted to evaluate the effects of high altitude on the pharmacokinetics of meperidine. Intramuscular doses (0.75 mg/kg) of meperidine were given to three groups of healthy volunteers (age range, 18-20 years): participants living at sea level (group L), those same participants the day after arrival at high altitude (4,360 m; group HA), and participants who had lived at high altitude for > or = 10 months (group HC). Blood samples were collected for 12 hours after drug administration. Meperidine was measured in whole blood, plasma, and plasma water. Elimination rate constant (lambda z) and clearance uncorrected for bioavailability (Cl/F) were significantly lower at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Mean residence time (MRT) was significantly higher at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Hematocrit was significantly increased at both time points at high altitude in comparison to values at sea level, and was also higher after a long-term stay at high altitude than after arrival at high altitude. Erythrocyte binding increased significantly from 41.3% at sea level to 43.8% at arrival at high altitude to 50.9% after a long-term stay at high altitude. The extent of protein binding tended to decrease with high altitude, but this decrease was not significant. Free concentrations of meperidine in plasma water measured 1, 2, and 4 hours after administration were significantly increased after 2 and 4 hours.

Adolescent↗
PubMed1996

Chronopharmacokinetics of theophylline administered as a controlled-release tablet.

The result obtained from different studies of the chronopharmacokinetics of some controlled-release tablets of theophylline are variable, since some authors report differences while others do not. At our laboratory we have developed a formulation of a controlled-release theophylline tablet using acrylic resins and we studied the chronopharmacokinetics of theophylline from this dosage form. Seven Caucasian healthy male volunteers participated in the study approved by the Institutional Review Board (IRB). Each volunteer received a controlled release tablet of 300 mg theophylline and an i.v. dose equivalent to 131.46 mg theophylline once at 8.00 a.m. and once at 8.00 p.m. Theophylline plasma concentrations were determined by HPLC. The following pharmacokinetic parameters were calculated: maximum concentration, time to reach maximum concentration, mean residence time, absorption constant, area under the curve of plasma concentration versus time, distribution volume (Vd beta), and total clearance. No statistically significant differences were found between diurnal and nocturnal data. This implied that, with this formulation, there is a lower risk of toxic plasma concentrations or concentrations under the therapeutic level than with formulations that exhibit circadian rhythm.

Adult↗
PubMed1995

Influence of ethanol ingestion on tetracycline kinetics.

The effect of ethyl alcohol ingestion on tetracycline kinetics was studied in 9 healthy male volunteers. They received, on two separate occasions, 500 mg of tetracycline tablets given with water or with an alcoholic beverage. The antibiotic was assayed in plasma, using a HPLC method. Absorption and disposition parameters were calculated according to classical pharmacokinetic techniques for one compartment model. The significance of changes in pharmacokinetic parameters was determined by a multiway ANOVA test. In the present study, ingestion of alcohol caused significant increase of Cmax (from 9.317 to 12.362 micrograms/ml), and increase of AUC (from 62.65 to 94.28 micrograms/ml*h).

Absorption↗
PubMed1995

Disposition kinetics of dibekacin in patients with renal failure and in patients undergoing hemodialysis.

Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 patients with renal failure presenting Clcr, between 4.0 and 67 ml min-1 per 1.73 m2 of body surface and 5 anephric patients given as a 30 minute intravenous infusion. The antibiotic was assayed in plasma and urine by means of a high performance liquid chromatography (HPLC) method. A two compartment kinetic model was used to describe the bi-phasic decline of plasma concentration and to calculate the different pharmacokinetic parameters. Slow disposition and elimination rate constants beta and k10 respectively, and total body clearance were markedly diminished in anephric patients (p << 0.001): t1/2 beta = 2.12 h, k10 = 0.642 h-1 and Cl = 0.882 ml/min per kg, in normal subjects and t1/2 beta = 4.73 h, k10 = 0.278 h-1 and Cl = 0.693 ml/min per kg in anephric patients. The apparent volumes of distribution increased while the creatinine clearance of the patients decreased. Thus Vd(area) of volunteers with normal renal function was statistically significantly lower than that of anephric patients (p < 0.001), from a value of 0.162 to 0.281 l/kg respectively. A good correlation (r = 0.982) between patient's slow disposition constant beta and creatine clearance was found. Urinary recovery at 24 h was 85.6% of the dose given to normal volunteers. This value decreased while impairment increased. The mean extraction coefficient, during hemodialysis was about 0.35.

Acute Kidney Injury↗
PubMed1993

Evaluation of the effect of different kinds of foods on the bioavailability of a sustained-release theophylline tablet.

Food-induced changes on the bioavailability of a sustained-release theophylline tablet, which uses acrylic resins Eudragit as sustaining agent, were studied in 12 healthy male volunteers. The tablet was developed in our laboratory using conventional technology. It presented a good bioavailability pattern and maintained plasmatic concentrations within the therapeutic range for 12 hours under conditions of steady-state. The study design was a 4 x 4 latin square involving 12 subjects who received a single dose of the tablet while fasting or with a standardized normal, high fat or high fat/high protein meal. The results showed no differences in AUC, K, tmax, ka and MRT. Statistical differences were found in Cmax comparing the fasting condition with high fat/high protein diet. A delay was also observed in the detection of the drug in plasma when the tablet was administered with high fat and high fat/high protein food, but clinically the changes seem to be irrelevant.

Absorption↗
PubMed1990

Influence of alcohol consumption on erythromycin ethylsuccinate kinetics.

The effect of ethyl alcohol ingestion on erythromycin kinetics was studied. Nine healthy volunteers, four males and five females, participated in the study. They received, in two separate occasions, 500 mg of erythromycin ethylsuccinate ester given with water or with an alcoholic beverage. The antibiotic was assayed in plasma, using a microbiological method. Absorption and disposition parameters were calculated according to classical pharmacokinetic techniques. A longer lag time and a decrease in AUC were observed when the antibiotic was given with alcohol. The differences were statistically significant. It is likely that the effect of alcohol on gastric emptying could be responsible for the delayed absorption of the antibiotic.

Adult↗
PubMed1990

Effect of mixing on the bioavailability of nitrofurantoin capsules.

The effect of blending time on the "in vivo" absorption of powder mixtures of similar composition, containing nitrofurantoin (NF), both in crystalline (10-50 u diameter) and macrocrystalline (70-80 u diameter) forms, was studied. The blending operations were performed using a Twin-Shell Blender (V-Type). The ingredients were blended long enough to obtain homogeneity, and this point was considered as "zero time". The mixing was continued and a intensifier bar was placed inside the blender. Samples were collected at 0; 30 and 45 minutes of blending and hard gelatin capsules were filled with these samples. A bioavailability study was performed in six healthy male volunteers. The experiments were conducted in a crossover fashion and each volunteer took one capsule of each time of blending of both microcrystalline and macrocrystalline nitrofurantoin. Urine samples were collected after the administration of the drug, and assayed by a spectro-fluorometric method. The total nitrofurantoin (NF) amount excreted in urine showed statistically significant differences at different times of blending only when capsules containing microcrystalline drug were administered.

Adult↗
PubMed1989

Design and evaluation of a controlled-release theophylline tablet. Preliminary communication.

A 300 mg controlled-release theophylline formulation was developed as a tablet prepared by wet granulation using the acrylic resins Eudragit S 100R and Eudragit RSPMR. The tablet was compared with a marketed controlled-release capsule using in vivo and in vitro tests. The in vitro dissolution of theophylline from the tablets followed an apparent zero order kinetics. The in vivo comparison was performed in a cross over fashion in four healthy volunteers who received one tablet or capsule every 12 hours during seven days. The results showed no statistically significant differences in AUC, tmax and in plasma theophylline concentrations at the different times. Nevertheless, concentrations were lower after the administration of the tablets than when the volunteers received the capsules. On the other hand, the apparent elimination half lives obtained after the tablets were longer than with the capsules. An excessive retardation in the release of theophylline from the tablet could be responsible for this fact.

Acrylic Resins↗
PubMed1989

Pharmacokinetics of a nitrofuran compound, nifurtimox, in healthy volunteers.

Nifurtimox disposition was evaluated in 7 healthy volunteers. Each subject received an oral dose of 15 mg/kg of nifurtimox and blood sample was obtained 11 h after the drug administration. We used an analytical method previously assessed in the literature. The pharmacokinetic analysis was carried out according to a one-compartment model and the most important parameters established were elimination half-life, distribution volume, and clearance. Serum concentrations were low in relation to the high doses administered. The low serum concentration is probably the result of a marked first pass effect.

Adult↗
PubMed1988

Amoxicillin kinetics and ethanol ingestion.

The effect of ethyl alcohol ingestion on amoxicillin kinetics was studied. Eight healthy volunteers participated in the study. They received, in three separate occasions, a 500-mg dose of the antibiotic given with water, hydroalcoholic solution or pisco-sour. Blood samples were drawn at appropriate intervals. Amoxicillin was assayed using a microbiological method. Absorption and disposition parameters were calculated by classical pharmacokinetic techniques. There were no statistical significant differences in the rate of elimination of the antibiotic in the three experimental conditions. Ethanol affected significantly the absorption rate constant, lag time and t peak. On the other hand, Cmax and AUC were not significantly modified. Thus, it can be concluded that ethyl alcohol has influence on the rate but not on the extent of absorption.

Adult↗
PubMed1988

Dose-dependent bioavailability of amoxycillin.

Amoxycillin bioavailability at four different dose levels was studied. Healthy volunteers participated in the experiments. They received in separate occasions a single 250 mg, 500 mg, 750 mg and 1 g doses of the antibiotic. Amoxycillin was assayed in the urine by microbiological method. The mean urinary recovery of amoxycillin was 59.6%, 55.9%, 58.5% and 45.8% of the given dose for the 250 mg, 500 mg, 750 mg and 1 g dose, respectively. Relative amoxycillin bioavailability was determined comparing the total amount of antibiotic excreted unchanged at 24 h of each dose to the 250-mg dose.

Adult↗
PubMed1987

Effect of structured dietary fiber on bioavailability of amoxicillin.

The effect of structured dietary fiber on the bioavailability of amoxicillin (AMX) was evaluated. Ten healthy volunteers ingested one of two isocaloric, isonitrogenous diets providing 7.8 gm/day (diet I) and 36.2 gm/day (diet II) of structured fiber for 3 days. Then they ingested one tablet (500 mg) AMX after breakfast. The other diet was administered for an additional 3 days and the study was repeated. Plasma and urinary AMX concentrations were measured at 9 and 24 hours, respectively, by a microbiologic technique. An open one-compartment model was used for pharmacokinetic analysis. AMX was absorbed more slowly when ingested with diet I than with diet II: the absorption rate constant was 1.04 +/- 0.37 and 1.75 +/- 0.75 (P less than 0.05); lag time for absorption was 0.34 +/- 0.13 hours and 0.29 +/- 0.11 hours (P less than 0.05). The first-order rate constant and elimination half-life were similar. Bioavailability was higher with diet I: the AUC was 12.17 +/- 3.04 vs. 9.65 +/- 2.64 micrograms/ml/hr with diet II (P less than 0.05). A higher content of dietary fiber increased AMX absorption rate and decreased the amount of drug absorbed.

Absorption↗
PubMed1987

Disposition kinetics of dibekacin in normal subjects and in patients with renal failure.

Dibekacin pharmacokinetics was studied in ten healthy volunteers and six patients with renal failure presenting Clcr less than 10 ml X min-1 per 1.73 m2 of body surface, given as a slow intravenous bolus to the volunteers and as a 30-minute intravenous infusion to the patients. The antibiotic was assayed in plasma and urine by means of a microbiological method using Bacillus subtilis. A two-compartment kinetic model was used to describe the bi-phasic decline of the plasma concentration thus establishing the different pharmacokinetic parameters. Elimination parameters beta, k10 and total body clearance were markedly diminished in renal patients (p less than 0.001): t1/2 beta was 2.0 h, k10 = 0.016 min-1 and Cl = 0.87 ml X min-1 kg body weight in normal subjects and t1/2 beta = 21.4 h, k10 = 0.0011 min-1 and Cl = 0.131 ml X min-1 per kg in the patients. Other kinetic parameters, as distribution (alpha) and transfer (k12, k21) constants were lower in patients than in volunteers. Also the different terms of volume of distribution of the two-compartment model (V1, Vdss, Vdarea) were significantly higher in patients than in normal subjects (p less than 0.05). A good correlation (r = 0.987) between patients' beta constant and creatinine clearance was found. A similar relationship between serum creatinine levels and disposition half-life was found (r = 0.955). Urinary recovery at 24 h was 89.0% of the dose given to normals and 15.8% of the dose given to patients.

Adult↗