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Biomedical subjects

A Arancibia

Publications and source records attributed to A Arancibia.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Pharmacokinetics and bioavailability of a controlled release amoxicillin formulation.

The pharmacokinetics and bioavailability of an in vitro controlled release amoxicillin formulation were studied in nine healthy volunteers, in comparison with an intravenous injection and a conventional tablet. The experiment was designed in a crossover fashion. The volunteers received the three formulations on separate occasions. The antibiotic was measured in plasma using a microbiological method. The absolute bioavailability of the two solid dosage forms was estimated comparing non-compartmental parameters. The results indicated that there was no correlation between the in vitro dissolution rate and the pharmacokinetic behavior in the body.

Adult↗
PubMed1987

Ranitidine disposition in severe hepatic cirrhosis.

The effect of severe liver disease on ranitidine disposition was evaluated by comparing its kinetics in 5 healthy subjects and 11 patients with alcoholic cirrhosis. Cirrhotic patients had severe liver disease as evidenced by the presence of ascites, hepatic encephalopathy, jaundice, muscle wasting, and low serum albumin, but creatinine clearance did not differ significantly between controls and cirrhosis. Following intravenous administration of ranitidine, systemic clearance was decreased in cirrhosis. These decrease may be associated with changes in renal function, and decrease in hepatic metabolism, usually present in patients with severe hepatic failure. The distribution volume of ranitidine was also decreased in cirrhotics, but the difference between patients and controls was not significant. Biological half-life was significantly longer in cirrhotic patients than volunteers. This difference may be due to decrease in total body clearance found in cirrhotic patients. It is concluded that patients with severe liver cirrhosis could have elevated plasma level of ranitidine and that a reduction of ranitidine dosage is warranted in these patients.

Adult↗
PubMed1986

Absorption and disposition kinetics of lithium carbonate following administration of conventional and controlled release formulations.

The absorption and disposition kinetics of lithium carbonate administered to eight healthy volunteers in two dosage forms were studied. A conventional immediate release tablet and a controlled release preparation, developed in our laboratory and containing the drug into a hydrophilic matrix, were employed in the study. Lithium carbonate confers upon the body the distinct characteristics of a two-compartment open model with a mean slow disposition rate constant (beta) of 0.0435 h-1 +/- 0.0086 SD, corresponding to a mean biological half-life of 16.49 h +/- 2.95 SD. The mean half-life of the distributory alpha-phase was 1.40 h +/- 0.27 SD. The apparent volume of distribution (Vdarea) was 0.539 l kg-1 +/- 0.130 SD and the volume of the central compartment (Vl) was 0.224 l/kg-1 +/- 0.066 SD, about one half that of the volume at steady state (Vdss) which was 0.445 l/kg-1 +/- 0.106 SD. Total body clearance (ClB) was 0.0241 l/kg-1 h +/- 0.0102 SD. The administration of the controlled release preparations to the same subjects gave the expected smooth serum lithium concentration curves. Maximum serum concentration (Cmax) was 22% lower and the time at which this concentration was attained (tpeak) was delayed from 1.44 h to 4.25 h when compared with the conventional tablet. Bioavailability, estimated as the total amount of lithium excreted in the urine, was 90.2 for the controlled release preparation and 94.5 for the immediate release tablet.

Adult↗
PubMed1986

Pharmacokinetics of gentamicin in children with nephrotic syndrome.

The disposition of gentamicin was studied in five children with nephrotic syndrome and five control children to observe the effect of nephrotic syndrome on the distribution and elimination of the antibiotic. After a single intravenous dose of gentamicin (2.0 mg/kg body wt.) administered to each child, blood samples were drawn at frequent intervals during a 4-h period and then analyzed by homogeneous enzyme immunoassay (EMIT). Time-concentrations drug profiles were characterized by means of a two-compartment open model. The mean half-life of gentamicin in nephrotic children (96.4 +/- 16.8 min) was significantly longer than in the control group (62.5 +/- 7.1 min). The distribution volume of the central compartment was similar in both groups studied, but the distribution volume at steady-state was increased in children with nephrotic syndrome. Total plasma clearance was found decreased in nephrotic (2.8 +/- 0.5 ml/min/kg) in comparison with controls (3.7 +/- 0.7 ml/min/kg). From our findings, it could be concluded that serum level of children with nephrotic syndrome treated with gentamicin should be carefully monitored in order to avoid the toxic effects of the antibiotic.

Child↗
PubMed1985

Pharmacokinetics of cimetidine in patients with liver disease.

Pharmacokinetics of cimetidine were studied after 200 mg i.v. doses in 7 patients with liver cirrhosis and in 10 healthy volunteers. Serial blood samples were obtained before and after drug administration over 12 hours. Cimetidine blood concentrations were determined by high pressure liquid chromatography (HPLC). The mean total body clearance in patients with cirrhosis (414.3 +/- 69.7 ml/min) was significantly less than that of subjects without liver dysfunction (501.1 +/- 37.9 ml/min) (p less than 0.01). However, the mean steady-state volume of distribution (1.34 +/- 0.41 l/kg vs 1.40 +/- 0.24 l/kg), volume of central compartment (0.51 +/- 0.11 l/kg vs. 0.45 +/- 0.05 l/kg), area volume of distribution (1.69 +/- 0.46 l/kg vs. 1.81 +/- 0.43 l/kg) and mean half-life (2.56 +/- 0.58 h vs. 2.68 +/- 0.43 h) did not demonstrate any significant changes. Renal clearance was significantly decreased from 389.5 +/- 41.9 ml/min in healthy subjects to 279.1 +/- 57.8 ml/min in cirrhotic patients (p less than 0.01). However, the mean extrarenal clearance was not changed in both groups. Modification of cimetidine dosage is therefore presumably not necessary in patients with compensated liver disease.

Adult↗
PubMed1984

The pharmacokinetics of cotrimoxazole sulphonamide in malnourished (marasmic) infants.

The pharmacokinetics of trimethoprim-sulphamethoxazole was examined in seven malnourished (marasmic) infants receiving cotrimoxazole (CMZ) for treatment of urinary tract infection. Comparisons were made with the SMZ level of ten nutritionally normal infants, hospitalized for first and second degree burns, receiving CMZ for treatment of bronchitis. CMZ was administered as an oral suspension (20 mg TMP and 100 mg SMZ, 5 ml), patients receiving 22 mg SMZ/kg body weight. Capillary blood samples, 0.05 ml were taken at prescribed intervals. Elimination half-life of SMZ in the marasmic infants was prolonged, 9.6 vs 4.9 hr, in their eutrophic counterparts. In addition, greater area under the curve (AUC), 573 vs 328 micrograms/ml/h, was noted in the malnourished group. This disparity may be due to differences in body fluid distribution between the two groups.

Drug Combinations↗
PubMed1983

Clinical pharmacokinetics of furosemide in children with nephrotic syndrome.

The pharmacokinetic disposition of furosemide has been investigated in seven children with nephrotic syndrome and in eight control children. Furosemide in plasma was analyzed by spectrofluorometry. After a single intravenous dose of furosemide (1 mg/kg body wt.) the nephrotic children showed lower initial plasma concentrations because of the larger volume of distribution. The mean half-life of furosemide in nephrotic children (38.5 +/- 7.8 min) was significantly longer than in the control group (28.0 +/- 7.7 min). The two groups did not differ in the body clearance of total furosemide. The average serum clearance was 4.95 +/- 1.7 ml/min/kg body wt. in the control group and 5.10 +/- 1.4 ml/min/kg body wt. in the nephrotic children. There was a significant reduction in urine sodium and distribution volume, whereas potassium excretion remained unchanged.

Child, Preschool↗
PubMed1982

Pharmacokinetics of furosemide in patients with hepatic cirrhosis.

The pharmacokinetics of furosemide was studied in 7 patients with diagnosed liver cirrhosis and in 7 healthy subjects. Furosemide in plasma and ascitic fluid was analyzed spectrofluorometrically. After a single intravenous dose, the cirrhotic patients showed lower initial plasma concentrations of furosemide because of the larger volume of distribution. The mean half-life in cirrhotic patients was significantly greater than in healthy volunteers. The longer half-life was associated with a reduction in the serum clearance of furosemide. Ascitic fluid volume in the patients ranged from 4.6 to 7.71. There was no significant amount of furosemide in the fluid. The diuretic interchange between this fluid and plasma was slow, as peak concentrations ranged from 0.3 to 0.5 microgram/ml within 3 to 5 h after bolus administration of furosemide. Diuresis and urinary sodium excretion, 5 h after furosemide injection, were similar in both groups; larger potassium excretion was found in the cirrhotic patients.

Adult↗
PubMed1982

Pharmacokinetics of amoxicillin in subjects with normal and impaired renal function.

The pharmacokinetics of amoxicillin was investigated in 4 healthy volunteers and in 16 patients with varying degrees of renal impairment, 4 of whom were on regular hemodialysis. Amoxicillin was administered both in a 1-g single intravenous injection and two 500-mg capsules per os. The kinetics of the antibiotic followed an open two-compartment model. In the patients with renal failure there was a significant decrease in beta, kappa10, and total body clearance. A linear relationship between beta of amoxicillin and creatinine clearance was found. This relationship allows dosage regimen adjustment for patients with renal impairment. A significant increase in the absorption half-life of the antibiotic was also observed in patients with renal impairment. The half-life of the antibiotic during hemodialysis was 2.3 h.

Aged↗