Biomedical subjects

Y Lou

Publications and source records attributed to Y Lou.

At least 37 records · Page 2Linked to original sources

PubMed2001

Abacavir/lamivudine/zidovudine as a combined formulation tablet: bioequivalence compared with each component administered concurrently and the effect of food on absorption.

A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg (A/L/Z) combination tablet relative to the separate brand-name components administered simultaneously and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 2-day washout period: one A/L/Z combination tablet after an overnight fast, one abacavir 300 mg tablet + one lamivudine 150 mg tablet + one zidovudine 300 mg tablet sequentially after an overnight fast, or one A/L/Z combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for determination of abacavir, lamivudine, and zidovudine serum concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals (CI) for geometric least squares (GLS) mean ratios for abacavir, lamivudine, and zidovudine area under the serum concentration-time curve (AUC(infinity)) and maximum observed serum concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined A/L/Z tablet was bioequivalent in the extent (AUC) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. GLS ratios and 90% CI for AUC(infinity) and Cmax were 0.99 (0.96, 1.03) and 1.00 (0.90, 1.11), respectively, for abacavir; 0.95 (0.91, 0.99) and 0.90 (0.84, 0.99), respectively, for lamivudine; and 0.95 (0.89, 1.02) and 0.96 (0.80, 1.15), respectively, for zidovudine. The extent of absorption of abacavir, lamivudine, and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of abacavir, lamivudine, and zidovudine. These changes, which were consistent with those observed with the individual reference formulations when administered with food, were not considered clinically important. All formulations were well tolerated underfasted and fed conditions.

Absorption↗

PubMed2001

Metabolic disposition and pharmacokinetics of [14C]-amprenavir, a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, administered as a single oral dose to healthy male subjects.

The objective of this study was to determine the metabolic profile, routes of elimination, and total recovery of amprenavir and its metabolites after a single oral dose of [14C]-amprenavir. Six healthy male subjects each received a single oral 630 mg dose of amprenavir containing 95.76 microCi of [14C]-amprenavir in this Phase I mass balance study. The metabolic disposition of amprenavir was determined through analyses of radiocarbon in whole blood, plasma, urine, and stool samples, collected for a period of 10 to 17 days postdosing. Cerebral spinal fluid (CSF) sampling was conducted on day 1. The ratio of unchanged amprenavir AUC0-->infinity to plasma radiocarbon was 27%, suggesting that most of the radiocarbon was metabolites. The median total recovery of the administered dose of radiocarbon was 89% (range: 66%-93%), with 75% (range: 56%-80%) recovered in the feces and 14% (range: 10%-17%) in the urine. Most of the recovered radiocarbon in the feces and urine was excreted within 240 and 48 hours postdose, respectively. Of the 75% of the radiocarbon dose recovered in the feces, 62% was identified as a metabolite resulting from dioxidation of the tetrahydrofuran ring (GW549445X) and 32% as a metabolite resulting from subsequent oxidation of the p-aniline sulfonate group (GW549444X). Unchanged amprenavir was below the limit of quantitation in feces and urine. Therefore, approximately 94% of the dose excreted in the feces was accounted for by these two metabolites. Concentrations of radiocarbon in the CSF were below the limit of quantitation in 5 of 6 subjects sampled. In summary, oral amprenavir is extensively metabolized in humans, with concentrations of unchanged drug below the limits of quantitation in urine and feces. The majority (75%) of administered radiocarbon was excreted in feces.

Administration, Oral↗

PubMed2001

[Effect of NPK and B supply levels on boron uptake and biological properties of different genotypic oilseed rape].

Pot experiment was conducted to study the boron absorption by oilseed rape(Brassica napus), the mechanism of its resistance to boron deficiency, and the effect of boron deficiency on its biological properties under different NPK supply levels. The results indicated that under boron deficiency, increasing NPK supply aggravated boron deficiency symptoms, which led to the decrease of leaf area and its growth rate and nitrate reductase activity(NRA) and the increase of chlorophyll(a + b) content at seedling stage, and the decrease of the number of productive branches and pods of each plant and seed yield at maturity. It was suggested that the ratio of boron concentration in youngest open leaves(YOL) to youngest mature leaves(YML) at seedling stage could be an index to judge the boron mobility in plants of different genotypic oilseed rape. Boron mobility and its utilization efficiency were one of the important nutritional mechanisms responsible for the difference in response of different genotypic oilseed rapes to boron deficiency.

Boron↗

PubMed2001

[Effect of boron fertilization on B uptake and utilization by oilseed rape(Brassica napus L.) under different soil moisture regimes].

Pot experiment was conducted in greenhouse to determine the effect of boron fertilization on B uptake and utilization by oilseed rape at seedling stage as influenced by soil moisture regime. The results showed that B concentration in shoot and root increased with the increase of soil water content and B fertilization level, while its utilization efficiency(BUE) and mobilization index(BMI) increased with the decrease of soil water content and B application level. Differences in BUE and BMI of test oilseed rape cultivars were significant, i.e., V1 showed higher BUE and BMI than V4 under the same conditions. It is concluded that BUE and B mobility in plant were the major factors responsible for the differences in response of different oilseed rape cultivars to B deficiency.

Absorption↗

PubMed2000

Determination of pharmacokinetics of 8-chloroadenosine and its two major metabolites in dogs by high-performance liquid chromatography.

High-performance liquid chromatography was used to measure concentration of 8-chloroadenosine (8-Cl-A) and its two major metabolites 8-chloroadenine (8-Cl-Ad) and 8-chloroinosine (8-Cl-I), and their pharmacokinetics in dogs. 8-Cl-A and its metabolites in serum were treated by deproteinization with acetonitrile, then organic impurities were extracted with dichloromethane, followed by centrifuged and direct injection of the supernatant into the liquid chromatograph. After intravenous injection of 8-Cl-A (30 mg/kg), the parent drug and 8-Cl-I were not detected, but the other metabolite, 8-Cl-Ad, was found at a high concentration for 240 min in dog serum. The main pharmacokinetic parameters of 8-Cl-Ad, t1/2beta and AUC, were 69.30 min and 580 microg min/ml. Our finding indicates that in dogs 8-Cl-A is rapidly metabolized and forms its major metabolites, 8-Cl-Ad and 8-Cl-I. 8-Cl-Ad appeared in many tissues, but 8-Cl-A and 8-Cl-I did not. The concentration of 8-Cl-Ad in dog tissues was highest in the liver and spleen, intermediate in the kidney, intestine, and lowest in the bone marrow, heart, and lungs. However, it was not detected in some liposoluble tissues such as the testes, brain, or uterus. Our study provides useful information for clinical experiment.

2-Chloroadenosine↗

PubMed2000

Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function.

Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(0-infinity)) showed an increase in amprenavir AUC(0-infinity) of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC(0-infinity) was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC(0-infinity). The relationship between the total bilirubin concentration and the AUC(0-infinity) of amprenavir was well characterized by a simple E(max) model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of alpha(1)-acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.

Adult↗

PubMed2000

Pharmacokinetic interaction between amprenavir and clarithromycin in healthy male volunteers.

The P450 enzyme, CYP3A4, extensively metabolizes both amprenavir and clarithromycin. To determine if an interaction exists when these two drugs are coadministered, the pharmacokinetics of amprenavir and clarithromycin were investigated in healthy adult male volunteers. This was a Phase I, open-label, randomized, balanced, multiple-dose, three-period crossover study. Fourteen subjects received the following three regimens: amprenavir, 1,200 mg twice daily over 4 days (seven doses); clarithromycin, 500 mg twice daily over 4 days (seven doses); and the combination of the above regimens over 4 days (seven doses of each drug). Twelve subjects completed all treatments and the follow-up period. The erythromycin breath test (ERMBT) was administered at baseline, 2 h after the final dose of each of the three regimens and at the first follow-up visit. Coadministration of clarithromycin and amprenavir significantly increased the mean amprenavir AUC(ss), C(max,ss), and C(min,ss) by 18, 15, and 39%, respectively. Amprenavir had no significant effect on the AUC(ss) of clarithromycin, but the median T(max,ss)for clarithromycin increased by 2.0 h, renal clearance increased by 34%, and the AUC(ss) for 14-(R)-hydroxyclarithromycin decreased by 35% when it was given with amprenavir. Amprenavir and clarithromycin reduced the ERMBT result by 85 and 67%, respectively, and by 87% when the two drugs were coadministered. The baseline ERMBT value did not correlate with clearance of amprenavir or clarithromycin. A pharmacokinetic interaction occurs when amprenavir and clarithromycin are coadministered, but the effects are not likely to be clinically important, and coadministration does not require a dosage adjustment for either drug.

Adolescent↗

PubMed2000

Population pharmacokinetics and pharmacodynamic modeling of abacavir (1592U89) from a dose-ranging, double-blind, randomized monotherapy trial with human immunodeficiency virus-infected subjects.

Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4(+) cell counts of >/=100/mm(3) and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (C(max)) and the area under the concentration-time curve from time zero to infinity (AUC(0-infinity)) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC(0-infinity). A significant correlation was observed between C(max) and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log(10) time-averaged AUC(0-infinity) minus baseline (AAUCMB) values for HIV-1 RNA and CD4(+) cell count correlated significantly with C(max) and AUC(0-infinity), but with better model fits for AUC(0-infinity). The increase in AAUCMB values for CD4(+) cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log(10) difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC(0-infinity) from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing.

Adolescent↗

PubMed2000

Multiple-dose pharmacokinetics and pharmacodynamics of abacavir alone and in combination with zidovudine in human immunodeficiency virus-infected adults.

Abacavir (1592U89) is a nucleoside reverse transcriptase inhibitor with potent activity against human immunodeficiency virus type 1 (HIV-1) when used alone or in combination with other antiretroviral agents. The present study was conducted to determine the multiple-dose pharmacokinetics and pharmacodynamics of abacavir in HIV-1-infected subjects following oral administration of daily doses that ranged from 600 to 1,800 mg, with and without zidovudine. Seventy-nine subjects received abacavir monotherapy for 4 weeks (200, 400, or 600 mg every 8 hours [TID] and 300 mg every 12 h [BID]) and thereafter received either zidovudine (200 mg TID or 300 mg BID) or matching placebo with abacavir for 8 additional weeks. Pharmacokinetic parameters were calculated for abacavir after administration of the first dose and at week 4 and for abacavir, zidovudine, and its glucuronide metabolite at week 12. The concentrations of abacavir in cerebrospinal fluid were determined in a subset of subjects. Steady-state plasma abacavir concentrations were achieved by week 4 of monotherapy and persisted to week 12. At steady state, abacavir pharmacokinetic parameters (area under the plasma concentration-time curve for a dosing interval [AUC(tau)] and peak concentration [C(max)]) were generally proportional to dose over the range of a 600- to 1,200-mg total daily dose. Coadministration of zidovudine with abacavir produced a small and inconsistent effect on abacavir pharmacokinetic parameters across the different doses. At the clinical abacavir dose (300 mg BID) zidovudine coadministration had no effect on the abacavir AUC(tau), which is most closely associated with efficacy. Zidovudine pharmacokinetics appeared to be unaffected by abacavir. Statistically significant but weak relationships were found for the change in the log(10) HIV-1 RNA load from the baseline to week 4 versus total daily AUC(tau) and C(tau) (P < 0.05). The incidence of nausea was significantly associated with total daily AUC(tau) and C(max). In conclusion, abacavir has predictable pharmacokinetic characteristics following the administration of multiple doses.

Adolescent↗

PubMed2000

[Antigen presenting role of dendritic cell proliferated from peripheral blood monocytes in patients with chronic hepatitis B].

OBJECTIVE: To study the presenting effect of dendritic cell (DC) proliferated from peripheral blood monocytes in patients with chronic hepatitis B on HBsAg. METHODS: DC proliferated from patient's peripheral blood monocytes by adding GM-CSF and IL-4 were incubated with HBsAg for 1.5h at different concentrations, then mixed with autologous T cell and cocultured in 96-well flat-bottomed microtiter plates for 5 d at 37 degrees C and 5% CO(2). (3)H-TdR was added 13h before the culture completion, and finally the cells were gathered and the cpm was tested. RESULTS: The proliferation of T cell by DC treated by HBsAg is significantly higher than untreated. CONCLUSION: DC cultured from peripheral blood monocytes in patients with chronic hepatitis B plays a role in presenting HBsAg.

Antigen Presentation↗

PubMed2000

[Studies on monoclonal antibodies of Magnaporthe grisea and its interfering effect on appressorium formation].

Selecting by indirect ELISA eleven hybridoma cell lines, secreting monoclonal antibodies (McAbs) against Magnaporthe grisea were produced by fusing mouse myeloma cells(SP2/0) with spleen cells from BALB/c mice immunized with the mixture of conidia, germ tubes and appressoria of M. grisea using 50% PEG. The result of IFTC test showed that four of McAbs, named as 2B4, 4A1, 1D1, and 2H4 specifically bound to the cell wall surface of the fungus; Western blotting revealed that 2B4, 4A1, 1D1 were recognized different protein antigens from the surface of conidia and germ tubes; These four McAbs could effectively interfere with the appressorium formation both on cellophane membrane and the surface of onion epidermis and inhibit the disease leaf lesions development in vitro test.

Animals↗

PubMed1999

Inhibitory effect of green and black tea on tumor growth.

The administration of green tea, black tea, or (-)-epigallocatechin gallate inhibited the growth of established nonmalignant and malignant tumors in tumor-bearing mice. In experiments with black tea, we found that its oral administration inhibited DNA synthesis and enhanced apoptosis in both nonmalignant and malignant tumors in tumor-bearing mice.

Animals↗

PubMed1999

Autoimmune ovarian inflammation triggered by proinflammatory (Th1) T cells is compatible with normal ovarian function in mice.

The detection of noninfectious ovarian inflammation (oophoritis) and serum ovarian autoantibodies in a patient with premature ovarian failure is indicative of an autoimmune etiology. The mechanisms of autoimmune ovarian injury leading to loss of function are currently unknown. In this study we investigated the impact of oophoritis on ovarian function based on two murine autoimmune ovarian disease (AOD) models. AOD can be induced by thymectomy at Day 3 after birth (d3tx). D3tx mice develop ovarian inflammation and atrophy with loss of oocytes. In these mice, ovarian atrophy and not oophoritis correlated with abnormal estrous cyclicity. The second AOD model is induced by active immunization of adult mice with a murine ZP3 peptide (pZP3) in adjuvant. After active immunization, the zona pellucida antibody titer, not oophoritis, correlated with reduced fertility. To investigate the effect of oophoritis in the absence of antibody response or ovarian atrophy, pZP3-specific T cells were passively transferred into naive syngeneic mice. This recruited cytokine-producing cells into the ovaries so that elevated cytokine production and its effect on ovarian function could be examined. Recipients of pZP3-specific T cells developed severe granulomatous oophoritis, and the diseased ovaries had elevated ovarian mRNA levels of interferon-gamma, interleukin-1beta, and tumor necrosis factor alpha. Despite these changes, fertility rates and gonadotropin-induced follicular development remained essentially normal. Therefore, normal ovarian function is compatible with severe ovarian inflammation mediated by autoreactive T cells.

Animals↗

PubMed1999

Safety and pharmacokinetics of abacavir (1592U89) following oral administration of escalating single doses in human immunodeficiency virus type 1-infected adults.

Abacavir (1592U89) is a nucleoside analog reverse transcriptase inhibitor that has been demonstrated to have selective activity against human immunodeficiency virus (HIV) in vitro and favorable safety profiles in mice and monkeys. A phase I study was conducted to evaluate the safety and pharmacokinetics of abacavir following oral administration of single escalating doses (100, 300, 600, 900, and 1,200 mg) to HIV-infected adults. In this double-blind, placebo-controlled study, subjects with baseline CD4+ cell counts ranging from < 50 to 713 cells per mm3 (median, 315 cells per mm3) were randomly assigned to receive abacavir (n = 12) or placebo (n = 6). The bioavailability of the caplet formulation relative to that of the oral solution was also assessed with the 300-mg dose. Abacavir was well tolerated by all subjects; mild to moderate asthenia, abdominal pain, headache, diarrhea, and dyspepsia were the most frequently reported adverse events, and these were not dose related. No significant clinical or laboratory abnormalities were observed throughout the study. All doses resulted in mean abacavir concentrations in plasma that exceeded the mean 50% inhibitory concentration (IC50) for clinical HIV isolates in vitro (0.07 microgram/ml) for almost 3 h. Abacavir was rapidly absorbed following oral administration, with the time to the peak concentration in plasma occurring at 1.0 to 1.7 h postdosing. Mean maximum concentrations in plasma (Cmax) and the area under the plasma concentration-time curve from time zero to infinity (AUC0-infinity) increased slightly more than proportionally from 100 to 600 mg (from 0.6 to 4.7 micrograms/ml for Cmax; from 1.0 to 15.7 micrograms.h/ml for AUC0-infinity) but increased proportionally from 600 to 1,200 mg (from 4.7 to 9.6 micrograms/ml for Cmax; from 15.7 to 32.8 micrograms.h/ml for AUC0-infinity. The elimination of abacavir from plasma was rapid, with an apparent elimination half-life of 0.9 to 1.7 h. Abacavir was well absorbed, with a relative bioavailability of the caplet formulation of 96% versus that of an oral solution (drug substance in water). In conclusion, this study showed that abacavir is safe and is well tolerated by HIV-infected subjects and demonstrated predictable pharmacokinetic characteristics when it was administered as single oral doses ranging from 100 to 1,200 mg.

Adult↗

PubMed1999

Safety and single-dose pharmacokinetics of abacavir (1592U89) in human immunodeficiency virus type 1-infected children.

Abacavir (formerly 1592U89) is a potent 2'-deoxyguanosine analog reverse transcriptase inhibitor that has been demonstrated to have a favorable safety profile in initial clinical trials with adults with human immunodeficiency virus (HIV) type 1 infection. A phase I study was conducted to evaluate the pharmacokinetics and safety of abacavir following the administration of two single oral doses (4 and 8 mg/kg of body weight) to 22 HIV-infected children ages 3 months to 13 years. Plasma was collected for analysis at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, and 8 h after the administration of each dose. Plasma abacavir concentrations were determined by high-performance liquid chromatography, and data were analyzed by noncompartmental methods. Abacavir was well tolerated by all subjects. The single abacavir-related adverse event was rash, which occurred in 2 of 22 subjects. After administration of the oral solution, abacavir was rapidly absorbed, with the time to the peak concentration in plasma occurring within 1.5 h postdosing. Pharmacokinetic parameter estimates were comparable among the different age groups for each dose level. The mean maximum concentration in plasma (Cmax) and the mean area under the curve from time zero to infinity (AUC0-infinity) increased by 16 and 45% more than predicted, respectively, as the abacavir dose was doubled from 4 to 8 mg/kg (Cmax increased from 1.69 to 3.94 micrograms/ml, and AUC0-infinity increased from 2.82 to 8.09 micrograms.h/ml). Abacavir was rapidly eliminated, with a mean elimination half-life of 0.98 to 1.13 h. The mean apparent clearance from plasma decreased from 27.35 to 18.88 ml/min/kg as the dose increased. Neither body surface area nor creatinine clearance were correlated with pharmacokinetic estimates at either dose. The extent of exposure to abacavir appears to be slightly lower in children than in adults, with the comparable unit doses being based on body weight. In conclusion, this study showed that abacavir is safe and well tolerated in children when it is administered as a single oral dose of 4 or 8 mg/kg.

Adolescent↗

PubMed1999

Abacavir: absolute bioavailability, bioequivalence of three oral formulations, and effect of food.

STUDY OBJECTIVES: Study A: to determine the absolute bioavailability of a single 300-mg abacavir hemisulfate tablet. Study B: to determine the bioequivalence of two oral abacavir formulations (300-mg hemisulfate tablet, 100-mg succinate caplet), the effect of food on the bioavailability of the 300-mg hemisulfate tablet, and the bioavailability of the hemisulfate tablet relative to the hemisulfate solution. DESIGN: Phase I, randomized, open-label, balanced two- (study A) and three- or four-period (study B), crossover studies. SETTING: Two clinical research centers. SUBJECTS: Six men infected with the human immunodeficiency virus (HIV), aged 27-39 years (study A), and 18 HIV-infected men and women, aged 21-50 years (study B). INTERVENTIONS: In study A, all subjects received a single, oral 300-mg tablet of abacavir hemisulfate or a single, intravenous infusion of abacavir hemisulfate 150 mg over 60 minutes. In study B, all subjects received each of three single-dose treatments: three 100-mg abacavir succinate caplets in a fasted state, one 300-mg abacavir hemisulfate tablet in a fasted state, and one 300-mg abacavir hemisulfate tablet with a high-fat breakfast. Twelve subjects in study B also received a fourth treatment of abacavir hemisulfate 300 mg as an oral solution in a fasted state. Plasma samples collected for 24 hours (study A) or 12 hours (study B), and urine samples collected for 12 hours (study A) were analyzed by validated high-performance liquid chromatographic methods. MEASUREMENTS AND MAIN RESULTS: Abacavir pharmacokinetic parameters were calculated using standard, noncompartmental methods. In study A, the geometric least square (GLS) mean absolute bioavailability of oral abacavir was 83% (range 65-107%). In study B, the hemisulfate tablet was bioequivalent to the succinate caplet, but its time to maximum concentration (Tmax) occurred 30 minutes earlier. Administration of the abacavir hemisulfate tablet with food had no effect on area under the curve from time zero to infinity (AUC0-infinity), decreased maximum concentration (Cmax) by 26%, and delayed Tmax by 38 minutes. The relative bioavailability (GLS mean AUC0-infinity ratio) of the 300-mg abacavir hemisulfate tablet to solution was 101%, Cmax was 11% lower, and Tmax was unchanged. The most common drug-related adverse events associated with abacavir were nausea, vomiting, abdominal pain, and headache, all of which were mild. CONCLUSION: Based on our results, abacavir is safe and well tolerated and can be administered with or without meals.

Administration, Oral↗

PubMed1999

Pharmacokinetic interaction between ketoconazole and amprenavir after single doses in healthy men.

STUDY OBJECTIVE: To determine the effects of coadministration of amprenavir and ketoconazole on the pharmacokinetics of both drugs, and to assess the utility of the erythromycin breath test (ERMBT) to predict and explain these effects. DESIGN: Open-label, randomized, balanced, single-dose, three-period crossover study. SETTING: University research center. SUBJECTS: Twelve healthy men. INTERVENTION: Subjects received amprenavir 1200 mg, ketoconazole 400 mg, and amprenavir 1200 mg plus ketoconazole 400 mg. Each treatment was separated by 14 days. MEASUREMENTS AND MAIN RESULTS: Serial plasma samples for amprenavir and ketoconazole concentrations were measured by high-performance liquid chromatography. Coadministration of the drugs increased amprenavir area under the curve extrapolated to infinity (AUCinfinity) by 31% and reduced its maximum concentration (Cmax) by 16%. Amprenavir increased the AUCinfinity of ketoconazole by 44% and increased the drug's half-life and Cmax by 23% and 19%, respectively. Both agents resulted in substantial inhibition of ERMBT. CONCLUSION: Coadministration of ketoconazole and amprenavir results in a statistically significant increase in AUC for both agents, but the changes are not likely to be clinically important.

Adult↗

PubMed1999

[An experimental study of anti-angiogenesis with a cartilage-derived inhibitor].

OBJECTIVE: To evaluate the efficacy of a cartilage-derived inhibitor for the treatment of corneal neovascularization in vivo. METHODS: A cartilage-derived inhibitor (CDI) from bovine scapula was purified to homogeneity. By rabbit corneal neovascularization (CNV) model, the effect of inhibition of CDI under various conditions was determined in corneal micropocket analysis. RESULTS: The purified CDI could inhibit strongly the growing speed and area of rabbit CNV compared to control (P < 0.001). CONCLUSION: It is demonstrated that CDI is a potent dose-dependent inhibitor of angiogenesis.

Angiogenesis Inhibitors↗