Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nelfinavir has been recently approved as a twice-daily (BID) dose regimen, but no evaluation of the influence of this regimen change on patients' protease inhibitor exposure has been published. The aim of this study was to compare trough plasma concentrations of nelfinavir obtained under the 1250-mg b.i.d regimen with the levels achieved with the original 750-mg three-times-daily (TID) regimen in 56 HIV-infected patients. Blood samples were obtained at steady state before the morning dose of nelfinavir. Plasma levels were measured by high-performance liquid chromatography. Eleven and 45 patients were following TID and BID regimens, respectively. Trough concentrations ranged from 0.14 to 11.74 mg/L and from 0.36 to 10.57 mg/L under TID and BID regimens, respectively. Large interpatient (coefficient of variation: 153%) and modest intrapatient (45%) variabilities of nelfinavir levels were observed. Twenty-one patients (38%) and six patients (11%) had levels above and below, respectively, the trough nelfinavir range (1.0--3.0 mg/L) recommended by the manufacturer. Trough levels are not affected by the dosing regimen; they mainly reflect the important interindividual variability, while remaining fairly stable over time. Many subjects had plasma levels repeatedly outside the assumed therapeutic range. Dose adjustment based on therapeutic drug monitoring may contribute to optimizing antiretroviral therapy.
Ther Drug Monit 2001 Aug
PMID:Nelfinavir plasma levels under twice-daily and three-times-daily regimens: high interpatient and low intrapatient variability. 1147 22

The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state paired plasma and saliva samples were obtained after approximately 1 week of treatment with 50-or 100-mg fluconazole as capsules. A significant correlation between plasma and salivary levels of fluconazole was observed. The median saliva/plasma concentration ratio was 1.3 and was independent of the ingested dose and the plasma fluconazole concentration. The prediction of fluconazole concentrations in plasma from the concentrations in saliva was, although unbiased, not precise. From these findings, the authors conclude that although stimulated salivary fluconazole concentrations are significantly correlated with plasma concentrations, it is not possible to predict plasma fluconazole levels from the salivary concentrations with adequate precision. However, saliva fluconazole concentrations have sufficient value to test for compliance and even semiquantitative prediction of plasma concentrations.
Ther Drug Monit 2001 Aug
PMID:Can fluconazole concentrations in saliva be used for therapeutic drug monitoring? 1147 32

Abacavir and amprenavir, a nucleoside reverse transcription inhibitor and a protease inhibitor, respectively, are new drugs used for the treatment of HIV. Methadone blood concentrations were measured in five addict patients receiving methadone maintenance therapy before and after introduction of abacavir plus amprenavir. The administration of these two drugs for a median period of 14 days resulted in a significant reduction (P = 0.043) of methadone concentration, with a median decrease to 35% of the original concentration (range 28-87%). Two patients reported on several occasions nausea in the morning before the intake of the daily methadone dose, which is compatible with withdrawal reaction to opioids. Because amprenavir is a cytochrome P4503A4 substrate and is involved in the metabolism of methadone, reduction of methadone concentrations could be explained by an induction of cytochrome P4503A4.
Ther Drug Monit 2001 Oct
PMID:Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir. 1159 3

The objective of this study was to develop and validate a limited sampling strategy (LSS) that allows accurate and precise estimation of the area under the plasma concentration versus time curve (AUC) of nevirapine, when used in the licensed dosage of 200 mg twice daily. Because nevirapine has a long plasma elimination half-life and the plasma concentration shows little variation within the 12-hour dosing interval, the authors also wanted to explore whether a time frame exists for which a single-sample LSS can be applied. Twenty HIV-1-infected individuals receiving steady-state treatment with nevirapine (200 mg twice daily) were enrolled. For the development of the LSS, 10 patients were randomly selected from the study population (index set). The pharmacokinetic results from the other 10 patients (validation set) were used for prospective validation of the proposed LSS. Blood samples were obtained before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours after ingestion. The relationship between the nevirapine concentration at each of the designated time points and the AUC 12h was evaluated by univariate and multivariate linear regression analysis. At each of the sampling times, a strong correlation was observed between the nevirapine concentration and the corresponding AUC 12h (r > 0.97). This allows for a single-sample LSS, using any time point during the dosing interval. When a single equation is preferred, the concentration of nevirapine in a random sample drawn 2 to 4 hours after ingestion of nevirapine (C 2-4h; in microg/mL) can be used for accurate estimation of the AUC 12h (in h x microg/mL) by using the equation AUC 12h (h x microg/mL) = 11.699 (h) x C 2-4h (microg/mL) - 4.381 (h x microg/mL). Validation of this equation resulted in a predicted AUC 12h that was nonbiased and very precise. These data show that the nevirapine concentration at each time point during the dosing interval can be used for accurate estimation of the AUC 12h. Even more practical, a sample obtained at any time between 2 and 4 hours after ingestion of nevirapine can be used. The authors therefore conclude that less intensive sampling (i.e., a single sample) can readily be used to assess the AUC 12h of nevirapine when used in a dosage of 200 mg twice daily.
Ther Drug Monit 2001 Dec
PMID:Limited sampling strategies for the estimation of the systemic exposure to the HIV-1 nonnucleoside reverse transcriptase inhibitor nevirapine. 1180 91

Highly active antiretroviral therapy, involving treatment with three or four antiretroviral agents, has greatly improved the effectiveness of therapy for human immunodeficiency virus (HIV) infection. It has also extended the number of possible drug interactions that may occur in treated patients. There are 105 possible two-drug interactions among the 15 currently approved antiretroviral agents. Well-characterized interactions involving inhibition of drug metabolism have been exploited to reduce dose size or frequency and to simplify treatment regimens. Many additional interactions are possible with other drugs used to treat or prevent complications of HIV infection. Interactions with methadone and other opiate abuse therapies are also of concern. The usefulness of therapeutic drug monitoring for antiretroviral drugs remains controversial. However, drug measurements before introduction of an interacting drug can establish patient-specific targets that can guide subsequent dosing adjustment.
Ther Drug Monit 2002 Feb
PMID:HIV drug interactions: the good, the bad, and the other. 1180 18

Heroin abuse is an international problem with which all countries must continually cope. Many countries have implemented heroin substitution therapy as an effective means of decreasing illicit heroin use, crime, HIV risk, and death, and in improving employment and social adjustment. Although methadone is the most commonly used medication for heroin substitution, other agonists in current use include levomethadyl acetate (LAAM), buprenorphine, and pharmaceutical-grade heroin. This report reviews toxicologic issues that arise in these programs. A broad array of testing methodologies are available that allow selection of on-site testing or laboratory-based methodology. Urine specimens may be monitored for nonprescribed drugs on a qualitative or semiquantitative basis. Methods for differentiating opiate sources by urinalysis have been proposed to distinguish poppy seed consumption from heroin abuse and for distinguishing pharmaceutical-grade heroin from illicit heroin. Therapeutic drug monitoring for methadone in plasma continues to be evaluated for use in establishing adequate dosing and detecting diversion, and new methods have been devised for measurement of the optical isomers of methadone in plasma. Biologic specimens, in addition to plasma and urine, have been evaluated for use in drug monitoring, including sweat, hair, and oral fluid, with promising results. Overall, the many recent developments in testing methodology provide more effective means to assess patients in heroin substitution programs and should contribute to improvements in public health.
Ther Drug Monit 2002 Apr
PMID:Toxicologic aspects of heroin substitution treatment. 1189 65

The interest in therapeutic drug monitoring (TDM) of antiretroviral drugs is growing rapidly. For the protease inhibitors, and to a lesser extent for the non-nucleoside reverse transcriptase inhibitors, relationships between plasma drug concentrations and their efficacy and toxicity have been identified. Furthermore, the pharmacokinetics of especially the protease inhibitors vary widely between patients, suggesting a role for TDM to individualize antiretroviral therapy. Recently, randomized, prospective clinical trials evaluating the role of TDM in the management of HIV-1-infected patients showed promising results. However, there are still many questions to be answered before large-scale introduction of TDM can be justified (e.g., which pharmacokinetic parameter should be optimized, and what is the minimal effective concentration). This review summarizes the basis for TDM of antiretroviral drugs and discusses the problems and prospects of this potential tool in the care for HIV-1-infected individuals.
Ther Drug Monit 2002 Jun
PMID:Critical issues in therapeutic drug monitoring of antiretroviral drugs. 1202 21

The authors investigated the steady-state plasma pharmacokinetics of nelfinavir in HIV-1-infected children in a dosage of 30 mg/kg every 8 hours and 45 mg/kg every 12 hours in 12 HIV-1-infected children (aged 2.1 to 10.8 years) participating in an open-label study of nelfinavir in combination with stavudine and lamivudine. Median values of the primary pharmacokinetic parameters of nelfinavir 30 mg/kg every-8-hours (n = 8) and 45 mg/kg every 12 hours (n = 10) were, respectively, for the area under the plasma concentration-time curve over 24 hours, 90.5 and 71.9 h x microg/mL, for the trough concentration 1.9 and 1.0 microg/mL, and for the maximal concentration 6.3 and 5.2 microg/mL. Overall, a 7-fold interpatient variability was observed for the exposure to nelfinavir. Nelfinavir 30 mg/kg every-8-hours or 45 mg/kg every 12 hours in HIV-1-infected children generally resulted in plasma concentrations higher than those obtained in adults. However, due to a large interpatient variability in the exposure, individual dosage adjustments based on plasma concentrations may be necessary for both dosing regimens to ensure optimal treatment.
Ther Drug Monit 2002 Aug
PMID:The pharmacokinetics of nelfinavir in HIV-1-infected children. 1214 31

The aim of the study was to asses influence of selected epidemiologic and virusologic factors on the course of chronic hepatitis C (CHC). Data obtained from 550 CHC patients was analyzed (F/M: 241/309; age: 14-87, average age: 44.9 +/- 15.6). HbsAg and HIV-positive, as well as patients taking drugs were excluded from the study. Progression of the liver disease was assessed by the maximal ALT activity, presence of clinical or histopathological symptoms of hepatic cirrhosis, and 363 liver biopsy results. Clinical and histological data was analyzed depending on: patients sex, age (= 40, and > 40 years old), portal of infection (history data on transfusion or another source of infection), history of HBV infection (presence or absence of anti-HBc antibodies), and HCV genotype (1b or no-1b group). HCV genotype was determined in 170 patients by the use of commercial InnoLipa kit (Innogenetics). Statistical analysis was based on t-Student test and chi-squared test with or without Yates correction. It was proved that in patients over 40 years old or with history of transfusion inflammatory activity and liver fibrosis activity are significantly higher than in the rest of patients. More advanced age, transfusion and history of HBV infection are risk factors for hepatic cirrhosis development in CHC patients. Neither patient's sex nor HCV genotype were found to have significant influence on the course of CHC.
Med Sci Monit 2001 May
PMID:Factors influencing natural history of chronic hepatitis C. 1221 22

The aim of our study was analysis of relation between HLA class II antigens and the liver disease severity in chronic hepatitis C (CHC) patients. The subject of analysis was data obtained from 134 CHC patients with disease confirmed by histopathologic test (F/M: 62/72; age 16-74; average age 41.4 +/- 12.7 yrs), HCV RNA-positive, HbsAg- and HIV-negative with no coexistence of any other liver diseases. Liver biopsy specimens were estimated according to Ishak's criterions (grading 0-18; staging 0-6). HLA DRB1 alleles were determined by a commercial method INNOLiPA DRB (Innogenetics, Belgium). Statistical analysis considered alleles occurring with frequency higher than 10%. The necroinflammatory activity (average grading score) was compared in groups of patients with- and without particular allele. The frequency of each allele's occurrence was analyzed according to patients sex, age and staging score of liver fibrosis. In statistical analysis t-Student test and chi-squared test with or without Yates' correction were applied. Statistically significant correlation was found between occurrence of DRB1*13 and DRB1*07 alleles and necroinflammatory activity intensification, and between occurrence of DRB1*13 allele and progression of liver disease. Mild liver damage, instead, expresses statistically significant relation with DRB1*11 allele.
Med Sci Monit 2001 May
PMID:DRB1 alleles in relation to severity of liver disease in patients with chronic hepatitis C. 1221 23


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