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Biomedical subjects

K Gallicano

Publications and source records attributed to K Gallicano.

15 recordsLinked to original sources
PubMed1996

Lack of gender effect on ciprofloxacin pharmacokinetics in humans.

The influence of gender on the single-dose pharmacokinetics of oral ciprofloxacin was investigated in a parallel designed study in 24 healthy, fasted volunteers. Ciprofloxacin (750 mg) was administered as a single tablet to 10 women and 14 men. All subjects were Caucasian except for one African American man. The mean age was 36 years for men and 33 years for women. Women received the drug during the nonmenstruating phase of their menstrual cycle and were not taking oral contraceptives at the time of the study. Plasma samples were collected over a 24 h period and assayed by h.p.l.c. The 90% confidence limits for the ratio of geometric means of maximum plasma concentration, apparent terminal half-life, and apparent oral plasma clearance (corrected for body weight) were between 80% and 125%, and those for the area under the plasma concentration-time curve were 71% and 101%. Results suggest that there were no gender-related differences in ciprofloxacin pharmacokinetics in men and nonmenstruating women of middle age.

Adult↗
PubMed1995

Effects of the antacids in didanosine tablets on dapsone pharmacokinetics.

OBJECTIVE: To investigate 1) the effects of the magnesium-aluminum antacids in didanosine tablets on dapsone absorption in healthy volunteers and 2) the effects of the antacid formulation of active didanosine tablets on dapsone pharmacokinetics in patients seropositive for human immunodeficiency virus (HIV). DESIGN: Two separate, randomized, two-period, two-treatment, crossover studies with a 21-day washout period between treatments. SETTING: Clinical investigation unit of a university hospital. PARTICIPANTS: Six healthy men and six HIV-positive men. MEASUREMENTS: Serial dapsone plasma concentrations were measured when dapsone, 100 mg, was administered alone and with either the third of four doses of didanosine placebo tablets (group 1) or the 27th of 28 doses of active didanosine tablets (group 2). In each study, pharmacokinetic variables were determined using noncompartmental methods and compared by analysis of variance. RESULTS: When dapsone was administered alone, pharmacokinetic variables did not significantly differ from those with dapsone given in either combination (P > 0.10 for all comparisons). CONCLUSIONS: Didanosine, antacids, and other excipients in the currently used didanosine chewable tablets did not significantly affect plasma concentrations of dapsone.

Absorption↗
PubMed1995

Pharmacokinetics of simultaneously administered zidovudine and didanosine in HIV-seropositive male patients.

Our objective was to determine whether a pharmacokinetic interaction exists between zidovudine and didanosine when they are coadministered. This was designed as a randomized, three-period, three-treatment, six-sequence, crossover study with a 1-week washout period between treatments. The patients were six men infected with human immunodeficiency virus who were asymptomatic. On three separate occasions, patients received zidovudine alone (200 mg every 8 h) for 3 days, didanosine alone (200 mg every 12 h) for 3 days, or zidovudine and didanosine for 3 days. On the fourth day, each patient received the final dose of each regimen, and blood and urine were serially collected for 8 h. Pharmacokinetic parameters were assessed for zidovudine, its glucuronide metabolite (GZDV), and didanosine. Coadministration of zidovudine had no significant effect on didanosine pharmacokinetic parameters (< 12% difference between treatment means, p > 0.1). Coadministration of didanosine did not significantly alter zidovudine pharmacokinetic parameters but did cause statistically significant increases in the renal and apparent formation clearances of GZDV (18.5% and 30.5% difference between the treatment means, respectively, p < 0.025). Therapeutic doses of zidovudine did not alter didanosine pharmacokinetic parameters. Coadministration of didanosine did not affect zidovudine parameters but did cause small alterations in GZDV pharmacokinetic values. These changes are unlikely to be clinically significant.

Adult↗
PubMed1995

Application issues in bioanalytical method validation, sample analysis and data reporting.

Although some degree of consensus has been reached concerning the requirements for acceptable method validation, the procedures used to establish them vary significantly between laboratories. Also, issues arising from application of these requirements during validation and subsequent sample analysis need to be addressed. The purpose of this paper is to discuss application issues concerning prerequisites to method validation, and all validation criteria for evaluation of method reliability and overall performance. Other poorly addressed issues such as re-validation, cross-validation, partial sample volume, multicomponent analysis and reporting will also be discussed. Although many issues discussed are of a general nature, the scope of this presentation is primarily to address issues arising from the validation and routine application of chromatographic methods.

Animals↗
PubMed1995

Effect of rifabutin on the pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus.

We investigated the effects of rifabutin (300 mg daily administered for 7 or 14 days) on the pharmacokinetics of zidovudine in nine patients who were infected with human immunodeficiency virus (HIV). Serial blood and urine samples were collected over a 6-hour period on each day that the pharmacokinetics of zidovudine were studied. Pharmacokinetic parameters were determined for zidovudine and its glucuronide metabolite and compared with use of analysis of variance (ANOVA) appropriate for a repeated-measures design. Except for a statistically significant decrease (28%) in the terminal half-life of zidovudine from 1.5 to 1.1 hours (P = .005) after coadministration of both agents for 14 days, concurrent administration of rifabutin for 7 or 14 days had no statistically significant effects on zidovudine plasma and urine pharmacokinetic parameters (the difference among treatment means was < 25%). Treatment with rifabutin is unlikely to influence the effectiveness of treating HIV-infected patients with zidovudine because of any pharmacokinetic interaction between these drugs.

Adult↗
PubMed1994

Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.

The effect of a therapeutic dose of fluconazole on the disposition of zidovudine was evaluated in 12 men infected with human immunodeficiency virus. The study was designed as a randomized, two-period, two-treatment, crossover trial. On two occasions, 21 days apart, patients received either zidovudine alone or zidovudine (each, 200 mg every 8 h) and fluconazole (400 mg daily) for 7 days. Fluconazole coadministration decreased (P < .001) the apparent oral serum clearance of zidovudine by 43% and the apparent oral formation clearance to zidovudine glucuronide (GZDV) by 48%, resulting in increases (P < .002) in the area under the serum concentration time curve (74%), the maximum serum concentration (84%), and the terminal half-life (128%) of zidovudine. The molar ratio of GZDV to zidovudine recovered in urine was reduced by 34% with fluconazole (P < .001). These pharmacokinetic changes suggest that 400 mg of fluconazole inhibited the conversion of zidovudine to GZDV. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions.

Adult↗
PubMed1994

Relationship between body weight, body surface area and serum zidovudine pharmacokinetic parameters in adult, male HIV-infected patients.

OBJECTIVE: To determine whether there is a simple relationship between body weight or body surface area (BSA) and serum zidovudine pharmacokinetic parameters in patients receiving oral zidovudine. DESIGN: Single-dose, pharmacokinetic study. PATIENTS: Fifty-three asymptomatic and symptomatic HIV-infected men (CD4+ cell count < 500 x 10(6)/l) participated in the study. Results of renal function and haematology tests were within normal limits and all hepatic function tests were up to three times the upper limit of normal. Patients received 200 mg oral zidovudine and serial blood samples were collected for 4 h (18 patients) or 8 h (35 patients). Serum zidovudine concentrations were measured by high-performance liquid chromatography (12 patients) or radioimmunoassay (41 patients). Pharmacokinetic parameters were calculated by non-compartmental methods. The relationships between body weight or BSA and maximum serum concentration (Cmax), area under the concentration-time curve (AUC), apparent serum clearance (CL/F), and apparent terminal volume of distribution (Vz/F) were determined by simple least-squares linear regression. RESULTS: There were no significant relationships between either body weight or BSA and Cmax, AUC, Vz/F (corrected for weight), and clearance (P > 0.07; R2 < 0.06 for all comparisons). A significant positive association between Vz/F, uncorrected for weight, and either weight (P = 0.011; R2 = 0.121) or BSA (P = 0.022; R2 = 0.098) was observed. The interindividual coefficients of variation of CL/F and Vz/F values were only marginally reduced when the parameters were corrected for weight (31.3 versus 30.8% and 28.0 versus 26.0% respectively). CONCLUSIONS: There is little or no linear association between either body weight or BSA and observed serum zidovudine concentrations following administration of 200 mg zidovudine in adult male patients who are within 20% of their ideal weight.

Adult↗
PubMed1994

Effect of antacids in didanosine tablet on bioavailability of isoniazid.

The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

Adult↗
PubMed1994

Effect of bismuth subsalicylate on ciprofloxacin bioavailability.

A single oral dose of 528 mg of bismuth subsalicylate (30 ml of Pepto-Bismol) had no significant effect on the plasma pharmacokinetics of a single oral dose of 750 mg of ciprofloxacin administered to 12 healthy volunteers (six men and six women). These results suggest that ciprofloxacin bioavailability will not be significantly decreased by single doses of bismuth subsalicylate when the two medications are administered simultaneously.

Absorption↗
PubMed1993

Cations in the didanosine tablet reduce ciprofloxacin bioavailability.

The effect of the magnesium-aluminum cations contained in didanosine chewable tablets on ciprofloxacin pharmacokinetics was evaluated in 12 healthy volunteers. The study was designed as a randomized, balanced, open, two-period, two-treatment crossover trial with a 7-day washout period between treatments. In one phase, subjects received a single 750 mg ciprofloxacin tablet alone. In the didanosinecation regimen, subjects received two didanosine-placebo tablets every 12 hours for two doses. On day 2, they received two didanosine-placebo tablets immediately followed by a single 750 mg ciprofloxacin tablet. Serial blood samples were collected for 24 hours after administration of each ciprofloxacin dose. The average maximum concentration of ciprofloxacin alone was 3.38 +/- 0.63 (SD) micrograms/ml compared with 0.25 +/- 0.21 (SD) micrograms/ml when ciprofloxacin was administered with the didanosine placebo (p < 0.0001). The mean (+/- SD) area under the plasma drug concentration-time curve from time 0 to the last measurable concentration for ciprofloxacin alone was 15.50 +/- 2.69 micrograms.hr/ml compared with 0.26 +/- 0.21 micrograms.hr/ml when ciprofloxacin was coadministered with the didanosine-placebo (p < 0.0001). The mean time to maximum concentration of ciprofloxacin alone decreased from 1.56 +/- 0.62 to 0.75 +/- 0.38 hours with buffer administration (p = 0.0012). The simultaneous administration of ciprofloxacin and didanosine should be avoided.

Adult↗
PubMed1993

Pharmacokinetics of zidovudine after the initial single dose and during chronic-dose therapy in HIV-infected patients.

The pharmacokinetics of zidovudine in 10 symptomatic HIV-infected men were assessed after administration of the initial 200 mg oral dose at the start of therapy (day 1) and on one occasion during non steady-state conditions of chronic-dose therapy (200 mg every 4 h while awake on day 21-66; 5 doses per day). The following mean (+/- s.d.) pharmacokinetic parameters were determined on day 1 and during chronic therapy, respectively: Cmax (4.09 +/- 2.54 vs 3.82 +/- 1.03 mumol l-1), oral clearance (40.7 +/- 12.9 vs 41.1 +/- 8.4 ml min-1 kg-1) and terminal half-life (68.4 +/- 29.4 vs 65.1 +/- 13.1 min). Mean pharmacokinetic parameters on day 1 were < 10% different (P > 0.34) from those determined during chronic therapy. Differences in means of 21% for clearance and 36% for Cmax could be detected with a power of 80% at the 5% significance level. Intra-subject coefficients of variation were 17% for clearance and 32% for Cmax, respectively. This study suggests that within a group of patients whose stage of HIV infection and general health are relatively stable, first-dose pharmacokinetic parameters provide a good estimate of multiple-dose pharmacokinetic parameters.

Administration, Oral↗
PubMed1992

Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.

OBJECTIVE: To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine. METHODS: This was designed as a randomized, two-period, two-treatment, crossover study. The patients were 12 men infected with human immunodeficiency virus who had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. On two separate occasions 14 days apart, patients received either zidovudine alone (200 mg every 4 hours while awake) or zidovudine (200 mg every 4 hours while awake) and naproxen (500 mg every 12 hours for 4 days). On the morning of the fifth day, each patient received the final dose of each regimen and blood and urine were serially collected for 8 hours. Pharmacokinetic parameters (area under the serum concentration-time curve [AUC], maximum plasma concentration, terminal half-life, renal clearance, and urinary recovery) were assessed for zidovudine and its glucuronide metabolite. MAIN RESULTS: Naproxen had no significant effect (< 10% difference between treatment means, p > 0.15, ANOVA) on the above pharmacokinetic parameters for both zidovudine and its metabolite. Although the power of the study to detect these small differences was < 80% at the 5% significance level, differences ranging from 12.6% for AUC to 38.8% for urinary recovery could be detected with 80% power. CONCLUSION: Therapeutic doses of naproxen do not significantly affect the pharmacokinetic disposition of zidovudine.

Adult↗
PubMed1992

The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients.

Eleven HIV-infected men participated in a randomized, two-treatment, two-period crossover study to determine the effect of a 25 g protein meal on zidovudine pharmacokinetics. On two separate occasions, 1 week apart, each patient received 200 mg zidovudine in a fasting state or immediately following the protein meal. A protein meal significantly decreased Cmax [532 (228 s.d.) vs 802 (452 s.d.) ng ml-1, P = 0.004] and increased mean residence time (138 (26 s.d.) vs 114 (26 s.d.) min, corrected for lag times, P = 0.001). However, AUC, tmax, terminal half-life and renal clearance were not significantly altered (P greater than 0.05). The power to detect a 20% change in AUC was 98% at the 5% significance level. In contrast to fat-containing foods, protein-based meals may not alter the extent of zidovudine absorption.

Dietary Proteins↗