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A Arancibia

Publications and source records attributed to A Arancibia.

At least 19 recordsLinked to original sources
PubMed2005

Pharmacokinetics of prednisolone in man during acute and chronic exposure to high altitude.

INTRODUCTION: The exposure to high altitude (H) produces several physiologic alterations which may induce changes in the pharmacokinetics of drugs. This hypothesis has been confirmed in previous studies which suggest that drugs which are highly bound to plasma proteins are most likely to exhibit altered pharmacokinetics. OBJECTIVES: To further elucidate the influence of H on pharmacokinetics, prednisolone was selected, since it is highly bound to plasma proteins, renally excreted and poorly bound to red blood cells. SUBJECTS, MATERIALS AND METHODS: Prednisolone (80 mg) was given orally to three groups of young healthy volunteers. One group was residing at sea level (L): the same volunteers were studied again after 15 hours of exposure to high altitude (3600 m, HA group), and volunteers living at H for at least six months (group HC). RESULTS: There were no statistically significant differences in the pharmacokinetic parameters calculated from plasma data in the three situations studied. When calculated from whole blood data, however, AUC and Cmax were increased and both volume of distribution and clearance diminished after exposure to H, either acute or chronically. Binding to proteins increased significantly after H exposure from 57% in group L to 75% and 94% in group H and HC, respectively. Binding to erythrocytes also increased with H exposure from 43.7% in group L to 50.6% and 61.6% in group HA and HC, respectively. The prednisolone/prednisone ratio in urine was 11.1 in group L, 7.3 in group HA and 45.6 in group HC. CONCLUSION: Since prednisone has very little intrinsic glucocorticoid activity and has to be converted to prednisolone for therapeutic effect, the alteration of the prednisolone/prednisone ratio, as a result of high altitude exposure could be clinically relevant. Additional experiments are desirable to further evaluate this observation.

Administration, Oral↗
PubMed2004

Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers.

INTRODUCTION: A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics. Our previous studies suggest that drugs highly bound to plasma proteins are most likely to exhibit altered disposition. OBJECTIVE: In continuation of our research, we selected furosemide which is about 98% bound to plasma proteins, renally excreted and has low binding to red blood cells. SUBJECTS, MATERIALS AND METHODS: Furosemide (40 mg) was administered orally to 3 groups of young healthy volunteers. One group who had been residing at sea level (group L), the same group after 15 hours of exposure to high altitude (3,600 m, group HA) and a group of volunteers living at H for at least 6 months (group HC). RESULTS: Our results are in accordance with the most recent pharmacokinetic studies on furosemide in which a terminal half-life of approximately 20-30 h was reported. Total proteins were 9.3% and 12.7% higher in groups HA and HC, respectively, than in group L. Albumin in group HC was 8.2% higher than group L. Bilirubin increased 17.7% and 41.2% in groups HA and HC, respectively, in comparison with group L. A rapid disposition rate constant in groups HA and HC was the only pharmacokinetic parameter that was significantly different from those in group L. Concentration of furosemide in plasma water increased significantly after H exposure, thus, the binding diminished from 97.2% in group L to 95.1% and 91.1% in groups HA and HC, respectively. CONCLUSION: Exposure to H produces an increase in the free fraction of furosemide in humans, which could be of therapeutic importance.

Adult↗
PubMed2003

Pharmacokinetics of lithium in healthy volunteers after exposure to high altitude.

INTRODUCTION: Exposure of the human body to high altitude causes a number of physiological changes. In previous studies, we observed that these changes may alter the pharmacokinetics of drugs. The number of erythrocytes/mm3 increases both, after acute exposure to high altitude (HA), i.e. within 12 - 24 h after reaching high altitude (H), as well as in chronic exposure (HC) (> 10 months) to H. Also binding of drugs to biologic material may change with exposure to HA and/or HC. OBJECTIVE: Since lithium is transported into and out of erythrocytes and binds strongly to erythrocytes, but is not plasma protein-bound, we selected this drug as candidate for the present study. SUBJECTS, MATERIAL AND METHODS: Lithium carbonate 300 mg were administered orally to young healthy volunteers. One group residing at low altitude (Santiago, Chile, 600 m, group L), these same volunteers after 15 hours of exposure to high altitude (4,360 m, group HA), and volunteers living at high altitude for at least 10 months (group HC). RESULTS: We found a significant increase of both hematocrit and red blood cell count (RBC) after exposure to H, both, acute or chronic. Elimination half-life increased 64.1% in group HA and 111.4% in group HC in comparison to group L. We also found an increase in volume of distribution: + 18.9% in group HA, and + 35.8% in group HC when measured in plasma, and + 16.9% in group HA and + 18.8% in group HC when measured in whole blood. Lithium uptake by the erythrocytes increases: the value of 36.7 +/- 22.7% in Group L rose to 54.8 +/- 21.1% and to 54.6 +/- 24.2% in groups HA and HC, respectively. Total clearance decreases at high altitude, though the differences were significant only in group HC (37%). CONCLUSION: Results indicate that exposure to H produces alterations in the pharmacokinetics of lithium and that these variations may be clinically relevant.

Administration, Oral↗
PubMed2003

Validated HPLC method for the determination of ranitidine in plasma.

A validated HPLC method for the determination of ranitidine in human plasma is presented. Sulfanilamide as internal standard (IS) was used. Plasma samples were purified by solid phase extraction (SPE) using a copolymeric [poly(divinyl-benzene-co-N-vinylpyrrolidone)] column ("Oasis Waters"). Mobile phase consisting of dibasic potasium phosphate 0.08 M/acetonitrile/methanol/triethylamine 0.05% (89.5:3:7:0.05) pH5 was used at a flow rate of 0.9 ml/min on a C18 column (Nova-Pack, 3,9 x 300 mm, Waters). The eluate was monitored using an UVNis detector set at 300 nm. Ratio of peak area of ranitidine to sulfanilamide was used for the quantitation of plasma samples. FDA criteria for bioanalytical validation was used to validate the method. Linearity was assessed between 100-1600 ng/ml, the limit of quantitation was 100 ng/ml and recovery was greater than 94%. Accuracy, precision and selectivity met the current recommendations for bioanalytical method validation. The method was successfully used in a bioavailability study of a ranitidine tablet in healthy volunteers.

Anti-Ulcer Agents↗
PubMed2001

[Acute cholangitis caused by choledocholithiasis: traditional surgery or endoscopic biliary drainage].

BACKGROUND: Endoscopic drainage of the biliary tree for acute cholangitis is a therapeutic modality with a lower mortality and complication rates. AIM: To compare endoscopic drainage with surgical treatment in the emergency management of acute cholangitis. PATIENTS AND METHODS: Between 1995 and 1998, sixty five patients with acute cholangitis were subjected to an endoscopic drainage of the biliary tree. In the same period, 40 patients were treated with traditional surgical procedures. The evolution of both groups of patients were compared. RESULTS: Sixty two patients (95.4%) subjected to endoscopic treatment had a satisfactory evolution, compared with 23 (58%) of those operated (p < 0.001). Five operated patients and no individual subjected to endoscopic drainage died (p < 0.01). Mean postoperative hospital stay of operated patients was 15.5 +/- 19.6 days compared to 5.8 +/- 4.2 days in those subjected to endoscopic drainage (p < 0.001). Definitive resolution of biliary obstruction was achieved in 83% of patients subjected to endoscopic drainage or traditional surgery. CONCLUSIONS: Endoscopic drainage has a lower rate of complications and mortality than traditional surgery, in the treatment of acute cholangitis.

Acute Disease↗
PubMed2000

Effect of three different diets on the bioavailability of a sustained release lithium carbonate matrix tablet.

BACKGROUND: Food-induced changes on the bioavailability of a sustained release lithium carbonate matrix tablet, which uses an acrylic matrix of Eudragit RSPM as sustaining agent, have been studied in healthy male volunteers. The tablet was developed in our laboratory using conventional technology. SUBJECTS, MATERIALS AND METHODS: 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. RESULTS: The results showed no differences in half-lifebeta, renal clearance, Vdbeta, AUC, tmax, Xinfinite(u), fraction absorbed and MRT. Higher Cmax (mg/l) were obtained when the tablet was administered with any kind of meal: 2.09 +/- 0.47 (fast), 2.95 +/- 1.04 (normal diet), 2.64 +/- 0.54 (high fat diet) and 2.87 +/- 0.67 (high fat/high protein diet). The analysis of the ratio Cmax/AUC indicated that changes in Cmax were more probably due to changes in the rate of absorption. To evaluate if the magnitude of the change could be clinically relevant, Cmax and C at 12 hours (dosing interval) were treated by the superposition method in order to establish maximum and minimum concentrations at steady-state. For all the experimental conditions both concentrations would remain in the therapeutic range (4.2 10 mg/l or 0.6 - 1.4 mEq/l). CONCLUSION: The behavior of the formulation is appropriate for a sustained release tablet and fasting or non-fasting state seems not to be a major consideration for bioavailability when deciding on the regimen administration.

Antimanic Agents↗
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↗