Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zidovudine (ZDV) elicits its antiviral effect through intracellular metabolism to the 5'-triphosphate, which interferes with viral replication. Monitoring of the active metabolites of ZDV in cells could lead to an intracellular therapeutic range. This study was performed to determine whether a radioimmunoassay, previously used for in vitro quantitation of total phosphorylated ZDV inside peripheral blood leukocytes, could be used for similar determinations in patient samples. The relationship between ZDV dose, plasma concentrations, and intracellular metabolite concentrations was also examined. Ten-milliliter blood samples were drawn from each of 13 human immunodeficiency virus-infected patients and were assayed. Intracellular concentrations of phosphorylated ZDV ranged from 0.33 to 3.54 pmol/10(6) cells, similar to those observed in vitro. Phosphorylated ZDV was independent of dose, and did not correlate with plasma concentrations. Intracellular concentration in the patient population as a whole did not change during the 4-h dosing interval, while plasma concentration decayed normally. Later determinations in the same patients gave intracellular values within 31% of earlier values. Intraassay variability was less than 10%. Thus, the method is valid for measurement of phosphorylated ZDV in patient cells. Although individual concentrations showed no clear change during the 3-month study period, intracellular concentrations decreased with increasing length of therapy (up to 3 years) in the population as a whole. This suggests a decreased cellular ability to phosphorylate ZDV after prolonged exposure to drug. The lack of intracellular decay implies a half-life longer than the 1-h half-life of plasma ZDV. These data suggest that smaller doses or longer dosing intervals might maintain intracellular concentrations once steady state is achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
Ther Drug Monit 1991 Jul
PMID:Concentrations of phosphorylated zidovudine (ZDV) in patient leukocytes do not correlate with ZDV dose or plasma concentrations. 178 Sep 65

Heat treatment of patient samples is utilized as a method to decrease the risk of accidental transmission of human immunodeficiency virus (HIV). Heat treatment has been reported to affect the outcome of drug analysis. In this study, the effects of heat treatment (56 degrees C for 5 h) and storage for 2 months at -20 degrees C on the stability of trimethoprim (TMP) and sulfamethoxazole (SMX) at three different concentrations in serum (10/100, 1/20, and 0.1/5 microgram/mL) each were evaluated. Simultaneous determination of TMP, SMX, and sulfamethazine (SMeth), the internal standard, in serum was performed by a reversed-phase high-performance liquid chromatographic (HPLC) procedure with isocratic elution and ultraviolet detection. The peak/height ratios (PHRs) for each sample from untreated and heat-treated groups were compared. No statistically significant differences were found between untreated and heat-treated groups for TMP. Heat treatment decreased the PHR for SMX at 100 micrograms/ml concentration (p = 0.042) and increased the PHR for SMX at 20 micrograms/ml concentration (p = 0.049). These marginal differences are unlikely to be significant. Storage of samples for 2 months at -20 degrees C had no statistically significant effect on sample PHRs. Thus, heat treatment of serum does not alter clinical interpretation of TMP and SMX at clinically relevant concentrations and may protect laboratory workers from accidental HIV exposure.
Ther Drug Monit 1995 Aug
PMID:High-performance liquid chromatographic evaluation of the effect of heat treatment on trimethoprim and sulfamethoxazole stability in serum. 748 89

Minimizing the risk of infection of laboratory staff from contaminated blood samples is a major safety goal in a clinical laboratory. One dangerous pathogen, the human immunodeficiency virus (HIV) can be deactivated by heating sera at 56 degrees C for 30 min. We studied the effect of such heat treatment on serum concentrations of 11 commonly monitored therapeutic drugs. We used blood specimens collected in serum separator tubes (SSTs), which were routinely submitted for therapeutic drug monitoring in our laboratory for this study. Concentrations of digoxin in sera were measured using a fluorescence polarization immunoassay (FPIA), while concentrations of tobramycin, gentamicin, vancomycin, theophylline, valproic acid, procainamide, N-acetylprocainamide (NAPA), phenytoin, phenobarbital, and carbamazepine were measured by enzyme-multiplied immunoassay technique assays using a Monarch 2000 analyzer. We observed no significant change in the concentration of any drug except phenytoin and carbamazepine following heating at 60 degrees C. The decrease in concentration of phenytoin and carbamazepine after heating was related to absorption of the drug to the gel rather than the instability of the drug under heating conditions. We conclude that blood contaminated with HIV may be deactivated by heating prior to analysis for most of the routinely monitored therapeutic drugs.
Ther Drug Monit 1994 Dec
PMID:Effect of heating sera under conditions necessary for deactivation of human immunodeficiency virus on commonly monitored therapeutic drugs. 787 3

Serum phenytoin concentrations were investigated in 109 serum samples from 21 patients with the acquired immunodeficiency syndrome (AIDS) and in 1,231 serum samples from 557 control subjects during phenytoin therapy. Total phenytoin concentrations were significantly lower in patients with AIDS than in the reference population (8.8 +/- 0.7 mg/L (mean +/- SE) vs. 10.6 +/- 0.2 mg/L), although phenytoin doses were significantly higher in the AIDS patients. Body weight and the use of folic acid were negatively related to phenytoin concentrations, whereas use of clarithromycin resulted in higher phenytoin levels. Zidovudine did not influence phenytoin levels. Calculation of the Michaelis-Menten parameters showed that Vmax values were similar in seven human immunodeficiency virus (HIV)-infected patients as compared with 12 controls, but a nonsignificant trend of lower Km values in the HIV-positive group was observed. Measurement of free phenytoin concentrations demonstrated that the fraction of unbound drug was increased in patients with AIDS. Hypoalbuminemia was common in this population, which may complicate the interpretation of total phenytoin concentrations.
Ther Drug Monit 1994 Dec
PMID:Therapeutic drug monitoring of phenytoin in patients with the acquired immunodeficiency syndrome. 787 4

Human immunodeficiency virus (HIV) may be transmitted via certain biological fluids, particularly blood. To minimize the risk of accidental exposure, the virus may be inactivated by heat treatment of blood, plasma, or serum samples at 54-56 degrees C for 5 h. The objective of this study was to determine whether heat treatment of human serum alters the protein binding of model compounds. Diazepam, phenytoin, and digitoxin were selected for investigation because they bind to three different sites on human serum albumin (HSA); propranolol also was examined since it binds to both HSA and alpha 1-acid glycoprotein. The unbound fraction of selected drugs was measured by ultrafiltration at 37 degrees C after addition of each compound to either untreated or heat-treated serum. The percentage unbound in serum for diazepam, phenytoin, digitoxin, and propranolol was not significantly different between the untreated and heat-treated samples. Therefore, heat treatment of serum does not appear to alter the binding characteristics at these four binding sites and would not be expected to lead to erroneous unbound concentration estimates and inappropriate adjustments in drug therapy.
Ther Drug Monit 1997 Aug
PMID:Heat treatment of human serum to inactivate HIV does not alter protein binding of selected drugs. 926 92

Seizures are common in patients infected with human immunodeficiency virus (HIV). Phenytoin and valproic acid are common anticonvulsants, and both drugs are strongly bound to serum albumin. Because patients infected with HIV are often on polytherapy, using homeopathic medicines, and may also have hypoalbuminemia, elevated free drug concentrations may occur in these patients. The authors prepared one serum pool from patients infected with HIV but receiving no bactrim and the other pool from HIV patients receiving bactrim. They supplemented both HIV pools and normal pool (diluted with 0.9% saline to mimic albumin concentration of HIV pools) with a known concentration of phenytoin or valproic acid. After incubation at 37 degrees C for 3 hours, they measured free phenytoin and free valproic acid concentrations in the protein free ultrafiltrates using fluorescence polarization immunoassays. The total drug concentrations in original sera were measured by microparticle enzyme immunoassays. None of the patients had any significant liver or renal disease. The aliquots of HIV pools and normal pool were supplemented with the same concentration of phenytoin or valproic acid. The concentration of free phenytoin and free valproic acid were significantly elevated in patients with HIV (mean = 2.52, SD = 0.11 micrograms/ml for phenytoin; mean = 41.5, SD = 1.5 micrograms/ml for valproate) compared to controls (mean = 1.50, SD = 0.0 7 micrograms/ml for phenytoin; mean = 19.9, SD = 0.5 micrograms/ml for valproate). The concentrations of both free phenytoin and valproic acid were further elevated in patients prepared in the HIV pool who were receiving bactrim (mean = 2.81, SD = 0.09 micrograms/ml for phenytoin; mean = 44.0, SD = 1.1 micrograms/ml for valproate), but when normal serum pool was supplemented with 4.4 mg/dl of bactrim (concentration of bactrim in HIV pool) and supplemented with the same concentration of phenytoin or valproic acid, the observed free concentrations were much lower (mean = 1.65, SD = 0.05 micrograms/ml for phenytoin; mean = 26.1, SD = 1.4 micrograms/ml for valproate). This indicates that hypoalbuminemia and bactrim concentrations do not account for the observed free drug concentrations in patients with HIV. The authors also observed elevated free phenytoin and valproic acid in sera from three individual patients with AIDS compared to normals (normal serum diluted with 0.9% saline to mimic the albumin concentration of serum collected from a patient with HIV and then both specimens supplemented with the same concentration of phenytoin or valproic acid.
Ther Drug Monit 1998 Feb
PMID:Elevated free phenytoin and free valproic acid concentrations in sera of patients infected with human immunodeficiency virus. 948 57

Recently, the authors were confronted with interference of stavudine and co-trimoxazole when analyzing the antiretroviral drug didanosine (ddI) in plasma of HIV-1-infected patients using reverse-phase high-performance liquid chromatography with ultraviolet detection. After increasing the percentage of methanol in the mobile phase from 4% to 8% vol/vol and after decreasing the pH of the mobile phase from 6.8 to 5.8, the authors were able to separate didanosine from stavudine and co-trimoxazole (both are frequently used drugs in combination with didanosine). Subsequently, the adapted bioanalytic methodology was validated, and validation results showed that this new methodology can be used for the quantitative determination of didanosine in human plasma. This observation makes clear that combination therapy for human immunodeficiency virus with multiple (often chemically related) drugs has the potential of unexpectedly complicating bioanalytic analyses because therapeutic strategies may change rapidly after publication of a bioanalytic methodology. Thus, it is evident that the investigation of interference of potentially coadministered drugs should be a standard procedure during the development of any bioanalytical methodology in any laboratory.
Ther Drug Monit 1998 Dec
PMID:Co-trimoxazole and stavudine interference in a high-performance liquid chromatographic analysis for didanosine in human plasma. 985 85

Efavirenz (EFV, DMP-266) is a new antiretroviral agent belonging to the class of nonnucleoside reverse transcriptase inhibitors. It has recently been approved by the Food and Drug Administration in management of human immunodeficiency virus (HIV). Preliminary pharmacokinetic studies on EFV in healthy volunteers show that the drug may influence the metabolism of protease inhibitors. For the determination of EFV in human plasma, a validated and specific reverse-phase high-performance liquid chromatography (HPLC) method, with UV detection, was developed. We used 100 microL plasma sample for a liquid-liquid extraction with diethyl ether after basification. The mobile phase was a mixture of acetonitrile and water, pumped at a flow rate of 1.2 mL/min. Ultraviolet detection was carried out at a wavelength of 247 nm. Retention times for EFV and internal standard (IS) were 5.3 and 4.5 minutes, respectively, and there was no chromatographic interference from other commonly administered drugs. The limit of detection was 100 ng/mL. The described assay is a rapid and accurate method for measurement of EFV in plasma: the easy preparation and small sample size makes this assay highly suitable for pharmacokinetic studies and routine clinical analysis in patients with HIV. In addition, the reproducibility of the method is only moderately increased by including IS, so analyzing without IS may be an alternative.
Ther Drug Monit 1999 Jun
PMID:High-performance liquid chromatography method for analyzing the antiretroviral agent efavirenz in human plasma. 1036 51

Minimizing the risk for infection to laboratory staff from a contaminated blood sample is a major safety goal in the clinical laboratory. One dangerous pathogen, the human immunodeficiency virus (HIV), can be deactivated by heating sera at 56 degrees C for 30 minutes. The authors previously reported that if serum was subjected to those conditions, the concentrations of the nine most commonly monitored drugs were not altered, whereas phenytoin and carbamazepine concentrations were reduced slightly. Monitoring free phenytoin, free valproic acid, and free carbamazepine concentrations is strongly recommended for patients with uremia, liver disease, and hypoalbuminemia. Because drug protein binding can be affected by temperature, the authors investigated the effect on free drug concentrations of sera heated to levels necessary for deactivation of the HIV virus. They measured total and free drug concentrations in serum pools prepared from patients receiving phenytoin, valproic acid, and carbamazepine. Serum pools were heated at 56 degrees C for 30 minutes and then brought to room temperature. The total and free drug concentrations were measured immediately after heating and then at 20- and 45-minute intervals. The concentrations of free phenytoin and free valproic acid were significantly higher after heat treatment. However, after equilibration of sera at room temperature for 20 minutes, the free concentrations of phenytoin were comparable to preheating values, although total phenytoin concentrations (Serum Separator Tubes) were reduced slightly. In contrast, free valproic acid concentrations did not return to the original levels even after 45 minutes. Free carbamazepine concentrations did not change even immediately after heating. However, total carbamazepine concentrations were reduced slightly when sera were heated in serum separator tubes (SST Tubes).
Ther Drug Monit 1999 Aug
PMID:Effect of heating human sera at a temperature necessary to deactivate human immunodeficiency virus on measurement of free phenytoin, free valproic acid, and free carbamazepine concentrations. 1044 96

A variety of medications are used in treating patients infected with the human immunodeficiency virus (HIV). These medications are used to control viremia and to prevent and treat opportunistic infections. An individual is often required to take numerous drugs at the same time and thus clinicians are confronted with potential drug interactions, some of which are significant. Three different groups of anti-HIV drugs are used to treat patients. These groups include nucleoside reverse transcription inhibitors, non-nucleoside reverse transcription inhibitors, and protease inhibitors. This article reviews the most relevant drug interactions that occur during the treatment of HIV-infected patients with traditional and also alternative drugs. The role of therapeutic drug monitoring in the routine management of HIV-infected patients is discussed.
Ther Drug Monit 2001 Dec
PMID:Pharmacokinetic and other drug interactions in patients with AIDS. 1180 90


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