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Biomedical subjects

S E Noormohamed

Publications and source records attributed to S E Noormohamed.

14 recordsLinked to original sources
PubMed2000

Semen and serum pharmacokinetics of zidovudine and zidovudine-glucuronide in men with HIV-1 infection.

STUDY OBJECTIVE: To characterize the concentration-time profiles of zidovudine and zidovudine-glucuronide in semen and serum of men infected with the human immunodeficiency-1 virus (HIV-1). DESIGN: Open-label observational study. SETTING: University-affiliated teaching hospital and research center. PATIENTS: Four asymptomatic HIV-1-infected men. INTERVENTIONS: Zidovudine administration was followed by an 8-hour intensive pharmacokinetic study on day 1. Over the next 8 days, a dose administration and timed single-sample strategy was employed to determine serum and semen concentration time profiles simultaneously. MEASUREMENTS AND MAIN RESULTS: Zidovudine and zidovudine-glucuronide concentrations were uniformly higher in semen than in serum except at 1 hour after the dose. The median area under the curve ratio (semen AUC0-48:serum AUC0-infinity) was 3.31 for zidovudine and 15.04 for zidovudine-glucuronide. CONCLUSION: Zidovudine and zidovudine-glucuronide reach high levels in seminal plasma relative to serum. The virologic, pharmacodynamic, and public health implications of distribution to this compartment require further study.

Adolescent↗
PubMed1998

Poor correlation between published methods to predict creatinine clearance and measured creatinine clearance in asymptomatic HIV infected individuals.

The purpose of this study was to evaluate the predictive ability of six published creatinine clearance (CCr) equations in healthy human immunodeficiency virus (HIV) infected individuals. A 24-h urine collection to determine CCr was done on an out-patient basis in 18 subjects. Predicted CCr was compared with the measured values, and the predictive performance was assessed with percentage mean error (bias) and percentage root mean error (precision). Mean +/- standard deviation measured CCr was 107 +/- 35 mL/min/1.73 M2. CCr determined using each of the published equations correlated poorly with measured values. CCr determined using Hull methods was significantly different from the measured values. Though Cockcroft and Gault and Jelliffe methods had the lowest mean bias and greater precision, a significant range of difference from measured CCr was observed (-12 to +28%). All methods over estimated the measured CCr in HIV-infected individuals. Until other approaches are developed, a 24 h urine collection may be the best approach for assessing renal function in HIV-infected individuals, especially in those receiving medications with narrow therapeutic indices that are cleared by the kidney.

Adult↗
PubMed1995

Strategies for control of zidovudine concentrations in serum.

There are several clinical scenarios in which knowledge of zidovudine disposition may be important. This study evaluated the clinical utility of pharmacokinetic parameters for zidovudine derived from sparse serum concentration data obtained in an outpatient setting. Twelve human immunodeficiency virus-infected participants had two serum zidovudine concentrations determinations obtained on two different clinic visits, 2 to 38 days apart. Zidovudine concentrations were measured by radioimmunoassay. A one-compartment oral absorption model was used to describe zidovudine disposition. Three different approaches were used to estimate pharmacokinetic parameters: Bayesian estimation with one or two concentrations and least squares with one concentration. The ability of these parameters to predict concentrations measured during the second clinic visit was assessed by calculation of precision and bias and compared with predictions using standard fixed or weight-adjusted parameters. Estimated pharmacokinetic parameters for zidovudine were consistent with literature values; there was no statistically significant difference among the parameters calculated with the three estimation strategies. Absorptive phase concentrations were poorly predicted by all methods (mean percent bias, 157 to 249%; mean percent precision, 389 to 537%). Predictive ability for concentrations obtained in the elimination phase was strikingly improved: mean percent bias, -17 to 70%; mean percent precision, 40 to 95%. Bayesian and least-squares estimated parameters were statistically better than fixed-parameter values for predicting concentrations in the elimination phase. These observations provide a modeling framework to determine pharmacokinetic disposition of zidovudine in an individual, screen for the existence of a drug interaction, and conduct concentration-controlled clinical trials.

Adolescent↗
PubMedDate not supplied

Alcohol use, drug use, and sexual activity among pharmacy students at three institutions.

OBJECTIVE: To determine alcohol and drug use and sexual activity among pharmacy students at three colleges of pharmacy. DESIGN AND SETTING: A survey to obtain self-reported information on alcohol and drug use, and sexual activity was administered to professional pharmacy students at the University of Iowa (UI), Massachusetts College of Pharmacy, and Texas Southern University. MAIN OUTCOME MEASURES: Information on sexual activity and condom use, alcohol and drug consumption, and the effect of alcohol on unintended sexual activity. RESULTS: 848 students (50% response rate) completed the survey. Alcohol use was high at all three institutions, and most students had consumed five or more drinks on one or more occasions within the last three months. The extent of drug use among pharmacy students was similar to that reported in other college students. The majority of students were sexually active. More men than women reported having been sexually active with one or more partners. Most students reported having had sexual intercourse without a condom. Significant numbers of students had engaged in unintended sex after alcohol use, especially at UI (chi 2 = 12.6, p = 0.002). Sexual contact and drinking were strongly correlated (Pearson r = 0.31, p = 0.0001). CONCLUSION: Alcohol consumption among pharmacy students was high. Heavy drinking (five or more drinks on one occasion) was associated with unintended sexual contact. Given low condom use and increased sexual contact, pharmacy students are at an increased risk for HIV infection. Strategies should be developed to reduce alcohol intake and unprotected sexual activity among pharmacy students.

Adult↗
PubMedDate not supplied

Evaluation of traditional African medicine "Compound R" for the treatment of thermal burn wounds in fuzzy rats.

The efficacy of an oil-in-water emulsion of a traditional Kenyan medicine, Compound R, on thermal burn wounds in fuzzy rats is reported. The burn wounds were inflicted on the depilated skin of rats with a 2 cm diameter aluminum template heated at 65 degrees C. Mean +/- SD days to healing (complete closure) were 9.9 +/- 2.2 (range 7 to 14 days) and 13.3 +/- 2.4 (range 10 to 16 days) for the treated and control (untreated) wounds, respectively (paired Student's t test, t value -5.667, p = 0.0003). Preliminary microbiologic results showed no activity of Compound R against some of the commonly encountered pathogens in burn wounds. Compound R appears to decrease the days to burn wound healing in fuzzy rats. This study provides preliminary data for further investigations of Compound R in managing burn wounds.

Administration, Topical↗
PubMedDate not supplied

Effect of 'Compound R' on thermal burn and full-depth wound contracture in fuzzy rats.

We evaluated the efficacy of Compound R emulsion on wound contraction in fuzzy rats. While the rats were under anesthesia, two mirror-image burn wounds were inflicted on the depilated back skin of each. Wounds were assigned randomly to treatment or placebo (oil), and the wound-scar areas were measured when they healed. A second set of wounds was created by taking two 6 millimeter punch biopsies from each rat and treated with Compound R or placebo. Under anesthesia, areas of the wound were measured on days 0, 5, 8 and on healing. Mean+/-SE areas for the healed burn wounds were: 151+/-24 mm2 for the treated and 102+/-26 mm2 for the placebo side (paired Student's t test, t=4.21, p=0.0015). Areas for Compound R-treated punch biopsy-induced wounds were significantly larger than placebo treated at each time point (p < 0.01). Results from this study show that Compound R impeded wound contraction.

Animals↗
PubMedDate not supplied

Recombinant erythropoietin for zidovudine-induced anemia in AIDS.

Recombinant erythropoietin (Epogen, Amgen Pharmaceuticals; Procrit, Amgen Pharmaceuticals, distributed by Ortho Biotech) is approved for use in anemia associated with HIV infection and treatment. The recommended starting dose is 100 IU/kg iv or sc 3 times per week. Current evidence suggests that anemia in zidovudine-treated patients may be a result of insufficient quantities of erythropoietin, bone marrow unresponsiveness to the hormone, or HIV infection. Among patients receiving zidovudine, a review of the available data suggests that baseline serum erythropoietin concentrations may aid in predicting the response to exogenous hormone administration.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Effect of erythromycin on ethanol's pharmacokinetics and perception of intoxication.

STUDY OBJECTIVE: To determine the effect of erythromycin on ethanol's pharmacokinetics and perception of intoxication. DESIGN: Double-blind, randomized, placebo-controlled, crossover study. SETTING: A clinical research center. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS: Erythromycin base 500 mg or identical placebo was administered 3 times/day for 7 days. On day 8, ethanol 0.8 g/kg was administered by mouth concurrently with erythromycin or placebo. A 2-week washout period was allowed between each treatment arm. MEASUREMENTS AND MAIN RESULTS: Twelve blood samples were obtained over a 12-hour period to determine ethanol concentrations. Perception of intoxication was determined at each time point using a 10-cm visual analog scale. Ethanol concentrations were determined using a gas chromatographic method. Mean +/- SD ethanol pharmacokinetics for erythromycin versus placebo were time to peak ethanol plasma concentrations 1.1 +/- 0.4 hours versus 1.3 +/- 0.3 hours, peak ethanol concentrations 118 +/- 18 mg/dl versus 114 +/- 27 mg/dl, ethanol oral clearance (CL/F) 2.9 +/- 0.8 ml/min/kg versus 3.4 +/- 2.2 ml/min/kg, and area under the curve 481 +/- 104 mg.hour/dl versus 465 +/- 132 mg.hour/dl (p > 0.05). The blood ethanol concentrations and perception of intoxication scores on a visual analog scale were well correlated (r2 = 0.78, p < 0.01). Mean +/- SD areas under the effect versus time curve were 35.1 +/- 20.7 cm/hour and 31.5 +/- 18.2 cm/hour for erythromycin and placebo, respectively (p > 0.05). CONCLUSION: Oral erythromycin base 1500 mg/day compared with placebo does not alter ethanol's pharmacokinetics or perception of intoxication in healthy volunteers.

Administration, Oral↗
PubMedDate not supplied

Effects of long-term drugs on alfentanil clearance in patients undergoing renal transplantation.

Although patients in renal failure frequently take several drugs on a long-term basis, drug-induced alterations in alfentanil metabolism have not been examined as a possible source of variability in alfentanil clearance in this population. We compared the pharmacokinetics of alfentanil during renal transplantation in seven patients receiving and six not receiving long-term drug therapy. After the rapid intravenous injection of alfentanil 100 micrograms/kg during isoflurane anesthesia, plasma concentrations were measured at intervals up to 6 hours by radioimmunoassay. The terminal elimination half-life, steady-state volume of distribution (Vdss), and total body clearance were determined by noncompartmental methods. There was no statistical difference in the Vdss between the two patient groups. However, clearance was significantly higher and elimination half-life lower in the group taking long-term drugs: clearance 6.94 +/- 4.64 versus 3.47 +/- 0.16 ml.kg-1.min-1, and elimination half-life 50.6 +/- 13.9 versus 90.7 +/- 22.4 minutes, respectively (p < 0.05). The higher clearance occurred even though five of the seven patients were taking agents known to be metabolized by the same cytochrome P-450 hepatic isozyme that metabolizes alfentanil and therefore potential competitive inhibitors of alfentanil metabolism. Drugs taken by the three patients with the highest alfentanil clearances included known inducers of hepatic drug metabolism. Thus, in the presence of several long-term drugs, the clearance of alfentanil appears to be noticeably increased by inducers of hepatic drug metabolism but unaffected by potential competitive inhibitors.

Adult↗
PubMedDate not supplied

The effect of cimetidine and ranitidine administration with zidovudine.

STUDY OBJECTIVE: To evaluate the possibility of a drug interaction with zidovudine and histamine2-receptor antagonists in individuals infected with the human immunodeficiency virus. DESIGN: Randomized crossover study. SETTING: University-affiliated research center. PATIENTS: Six HIV-infected individuals. INTERVENTIONS: The subjects received 7-day regimens of zidovudine 600 mg/day alone, zidovudine with cimetidine 1200 mg/day, and zidovudine with ranitidine 300 mg/day. MEASUREMENTS AND MAIN RESULTS: The renal clearance of zidovudine when given alone was 0.41 L/kg/hour, and was reduced to 0.18 L/kg/hour (p = 0.002) when given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 microM (p = 0.01), the urinary ratio of metabolite to parent increased from 5.16 to 9.96 (p = 0.0001), and the fraction of zidovudine converted to metabolite increased from 0.86 to 0.92 (p = 0.0025). CONCLUSION: Cimetidine presumably inhibits the renal clearance of zidovudine by competing for tubular secretion. Based on the observation that neither cimetidine nor ranitidine had a significant effect on serum concentrations of zidovudine or zidovudine glucuronide, a change in the dosage of zidovudine is not warranted.

Adolescent↗