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PubMed1990

Probenecid inhibits the metabolic and renal clearances of zidovudine (AZT) in human volunteers.

The effect of probenecid on the disposition of AZT was investigated in a pilot study in two healthy volunteers. The pharmacokinetics of AZT were examined after a single oral dose of 200 mg with and without probenecid coadministration in a balanced crossover study. Administration of 500 mg probenecid every 6 hr prior to and during AZT dosing resulted in an increase in the average AUCAZT from 89 micrograms.min/ml (control) to 191 micrograms.min/ml during probenecid treatment. This was manifested by a corresponding decrease in CLTOT/F, which is attributed to the inhibitory effect of probenecid on the glucuronidation and renal excretion of AZT. Average CLR and CLTOT/F of AZT decreased from 4.76 and 28.7 to 2.98 and 14.1 ml/min/kg during control and probenecid treatment, respectively. AZT glucuronidation was affected to a greater extent than its renal excretion, as reflected by the decreased ratio of GAZT/AZT urinary recoveries. The terminal half-life of AZT was slightly longer during probenecid administration. That only a small change in the half-life occurred indicates that probenecid also reduced the volume of distribution of AZT. The CLR of GAZT decreased from an average of 11.3 ml/min/kg (control) to 2.63 ml/min/kg during probenecid treatment, resulting in a greater than 3.5-fold increase in AUCGAZT. Probenecid did not affect the blood/plasma distribution or the plasma protein binding of AZT. These preliminary findings suggest that it may be possible to maintain effective plasma AZT concentrations in AIDS patients receiving a reduced daily dose, in combination with probenecid.

Adult↗

PubMed1991

The bioavailability and nonlinear clearance of (-)-carbovir in the rat.

The pharmacokinetics and bioavailability of (+/-)-carbovir, a carbocyclic nucleoside active against human immunodeficiency virus, have been described previously. To determine the bioavailability of (-)-carbovir, the biologically active enantiomer, four male Sprague-Dawley rats received 18 mg/kg of (-)-carbovir through the jugular vein and 54 mg/kg orally. Following the pilot studies, five rats were randomly assigned to receive (-)-carbovir in a three-way crossover design as either a single 18-mg/kg iv bolus, a single 54-mg/kg oral dose, or a single iv infusion of 18 mg/kg to achieve a target steady-state concentration (Css) of 1 micrograms/ml, the peak concentration after an oral dose. Blood and urine samples were analyzed by an improved ion-paired reversed-phase HPLC method with fluorescence detection. Blood concentrations of (-)-carbovir declined in a biphasic manner after the iv bolus dose. The terminal half-life was 116 and 106 min after the iv bolus and oral dose, respectively. The blood/plasma distribution ratio was approximately 1.0 in the range of 1 to 10 micrograms/ml of (-)-carbovir in blood. The free fraction in serum was concentration dependent. Significant differences in the renal, nonrenal, and total-body clearances after the iv bolus and iv infusion suggested nonlinear elimination of (-)-carbovir. The oral bioavailabilities derived from blood data were significantly different when the iv bolus was used as a reference rather than the iv infusion. However, the bioavailabilities were not significantly different when the total urinary excretion of unchanged (-)-carbovir after iv bolus or infusion was used as a reference.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Decreased systemic clearance of diltiazem with increased hepatic metabolism in rats with uranyl nitrate-induced acute renal failure.

The effect of uranyl nitrate (UN)-induced acute renal failure (ARF) on the pharmacokinetics of diltiazem (DTZ) was examined in rats through in vitro and in vivo studies. In vitro homogenate studies demonstrated that DTZ was metabolized to deacetyl diltiazem (DAD) predominantly in the liver. Metabolism in the small intestine, kidney, or blood pool was negligible compared with that in the liver. UN-induced ARF (UN-ARF) increased the in vitro hepatic clearance (CLvit) of DTZ 1.4-fold. In vivo pharmacokinetic studies following intravenous (iv) and portal venous (pv) administration revealed that UN-ARF increased the intrinsic clearance (CLi) of DTZ from 243.0 to 414.5 ml/min/kg but decreased its total plasma clearance (CLt) from 90.3 to 64.3 ml/min/kg. The increase in CLi was consistent with the increase in CLvit of the liver. The in vitro plasma free fraction of DTZ (fp) was decreased from 0.25 to 0.14 by UN-ARF, but the in vitro blood/plasma partition of DTZ (Rb) remained constant at unity. From the CLi and fp changes, the plasma intrinsic clearance for unbound DTZ (CLi') was calculated to be increased 2.7-fold, from 1104.5 to 2960.7 ml/min/kg, by UN-ARF. The fp decrease was also reflected in the steady-state distribution volume (Vdss) of DTZ, which was decreased significantly from 3595.5 to 2528.3 ml/kg. The absolute bioavailability of pv DTZ (Fpv) was decreased by UN-ARF from 37.5 to 15.5% but was still much higher than the reported oral bioavailability (6%), indicating poor absorption of DTZ from the GI tract. From the calculation based on a well-stirred pharmacokinetic model, DTZ was found to increase the hepatic blood flow (HBF) of the control rats more than twofold at doses of 3 mg/kg (iv) or 10 mg/kg (pv), possibly due to the vasodilating effect of DTZ. However, the effect of DTZ on HBF was not present in the UN-ARF rats. It is not clear at present whether this could be attributed to vasoconstricting effects of UN-ARF or blockade of the vasodilating effect of DTZ.

Acute Kidney Injury↗

PubMed1991

Extent and variability of the first-pass elimination of adinazolam mesylate in healthy male volunteers.

The pharmacokinetics of adinazolam and N-desmethyladinazolam (NDMAD) were studied in 14 healthy male volunteers who received 15 mg adinazolam mesylate orally as a solution and 5 mg adinazolam mesylate intravenously in a crossover design. Two weeks prior to the crossover study, each subject received 5 mg/kg indocyanine green (ICG) as an intravenous bolus injection to estimate liver blood flow. The absolute bioavailability (F), calculated as the dose-corrected ratio of oral to iv adinazolam area under the curve (AUC) values, was found to be 39%. NDMAD AUC values were similar following oral and iv administration, and adinazolam mean absorption time was approximately 0.77 hr. Thus, adinazolam is completely and rapidly absorbed after oral administration in man; the incomplete bioavailability is due to first-pass metabolism. Mean liver blood flow, adinazolam systemic clearance, blood/plasma ratio, and extraction ratio were 1189 ml/min, 498 ml/min, 0.70, and 0.57, respectively. The extraction ratio agrees with that calculated as 1-F (0.62), suggesting that the liver is primarily responsible for first-pass metabolism of adinazolam. The unbound fraction of adinazolam in plasma was 0.31 (range, 0.25-0.36); adinazolam free intrinsic clearance (a reflection of metabolic capacity) was 4285 ml/min (range, 2168-6312 ml/min). These results suggest that the majority of the variability in adinazolam plasma concentrations following oral administration is due to the variability in the metabolic capacity of the liver for adinazolam, rather than variability in plasma protein binding.

Adult↗

PubMed1980

Disporition of synthetic glucocorticoids. II. Dexamethasone in parturient women.

The plasma level: time profile for dexamethasone after dexamethasone phosphate 8 mg by intravenous bolus (n = 6) or intramuscular injection (n = 6) to pregnant women near term who were to undergo cesarean section was determined by high-performance liquid chromatography. Although pregnancy did not affect the terminal half-life (mean, 142 min; n = 10), the estimate of total plasma clearance was greater in pregnant (559 ml/min) than in nonpregnant women (243 ml/min). The umbilical/maternal venous plasma level ratios of dexamethasone rose with time from last dose to delivery, toward a plateau value of about 0.45. Plasma binding was not different between blood from pregnant (66.6% bound, n = 11) and nonpregnant women (68.1% bound, n = 6) but was lower in umbilical vein blood (60.8% bound, n = 11). Blood/plasma level ratio was higher in maternal (0.92, n = 7) and umbilical vein blood (1.04, n = 7) than in blood from nonpregnant subjects (0.81, n = 12). We conclude that the fetus is a slowly equilibrating compartment for dexamethasone and that the transplacental dexamethasone concentration gradient as well as the increased total clearance in the mother near parturition are most likely attributable to metabolic clearance by the placenta.

Adult↗

PubMed1982

Dipyridamol kinetics.

The kinetics of the antiplatelet drug dipyridamole were studied in six normal subjects (three men and three women) who were ages 22 to 34 yr old. Each received 20 mg IV and four also took a 50-mg oral dose. Blood samples were collected after each dose for a period of 3 days and concentrations of dipyridamole were measured by a sensitive and specific high-performance liquid chromatographic assay. Concentrations after the intravenous dose showed a triexponential decline with a terminal half-life of 11.6 +/- 2.2 hr (x +/- SD). Total plasma clearance was 8.27 +/- 1.82 1/hr and the apparent volume of distribution was 141 +/- 51 1. Concentrations rose 6 to 10 hr after intravenous dipyridamole in each female subject, but not in the male subjects. Dipyridamole blood/plasma concentration ratio changed from an average of 0.7 over the first hour to 1.2 after 5 hr after the intravenous dose. There was an absorption lag time ranging from 34 to 75 min after the oral dose; concentrations peaked at about 2 to 2.5 hr after the dose. The percentage of unbound drag in plasma was 0.88 +/- 0.24%. Systemic availability of the end oral dose was 43 +/- 13%. These results suggest widely varying concentrations in patients receiving the drug, and raise questions about the current clinical practice of using empirical dosage schedules.

Administration, Oral↗

PubMed1982

Phencyclidine disposition after intravenous and oral doses.

[3H]-Phencyclidine (PCP) hydrochloride was given in intravenous (0.1 or 1 mg) or oral (1 mg) doses to male subjects. After 1 mg IV, drug and metabolites were recovered in urine (72.8 +/- 4.0% of dose), feces (4.7 +/- 0.9%), and perspiration. Fecal excretion was low (3.4 +/- 0.4%) after oral dosing and oral bioavailability was estimated at 72%. PCP comprised 16% of urinary radioactivity with 31% consisting of enzymatically hydrolyzable conjugates of hydroxylated metabolites. Both cis and trans isomers of 4-phenyl-4-(1-piperidinyl)cyclohexanol were found. Maximum average plasma PCP concentrations of 2.7 to 2.9 ng/ml were observed after oral and intravenous 1-mg doses. Blood/plasma ratios were approximately 1.0 and plasma binding was about 65%. Parent drug was found in saliva. Apparent terminal phase half-lifes averaged 21 +/- 3 hr (harmonic mean 17 hr, range 7 to 46 hr). The volume of distribution averaged 6.2 +/- 0.3 l/kg. Renal clearances were variable, but the average was 9% of the total clearance. Thus, PCP is cleared principally by metabolism.

Administration, Oral↗

PubMed1985

Effects of age on meperidine disposition.

Elderly patients appear to be more sensitive to meperidine than younger ones; however, the contributions of altered dynamic and kinetic factors are not clear. Accordingly, seven healthy normal men aged 60 to 79 yr were simultaneously given 25 mg meperidine HCl intravenously and the same dose of deuterium-labeled drug either orally or intramuscularly (deltoid). Blood and urine samples collected over 24 hr were analyzed by gas chromatography-mass spectrometry and kinetic data were compared to those previously obtained in a young cohort. Systemic clearance (8.61 +/- 2.22 ml/min/kg), apparent oral clearance (17.5 +/- 5.5 ml/min/kg), terminal t1/2 (6.98 +/- 1.86 hr), and the blood/plasma concentration ratio (0.97 +/- 0.12) in the elderly did not differ from those in younger subjects. In the elderly, however, the initial (2.4 +/- 0.8 l/kg) and the steady-state (4.6 +/- 0.9 l/kg) volumes of distribution were 300% and 135% values in the young. No age differences were found in absorption profiles or bioavailability after oral (F = 0.49 +/- 0.08) or intramuscular (F = 0.94 +/- 0.04) dosing. It appears that age-related alterations in drug disposition per se do not account for changes in clinical efficacy of meperidine in the elderly.

Administration, Oral↗

PubMed2006

Evalution of the castrated male Sprague-Dawley rat as a model of the metabolic syndrome and type 2 diabetes.

OBJECTIVE: Low testosterone levels have been shown to be predictive for the development of the metabolic syndrome in men. The aim of this study was to describe effects of testosterone deficiency on metabolic syndrome-related parameters in male rats in order to evaluate the rat as a model for the human metabolic syndrome related to low testosterone levels. METHODS: Male Sprague-Dawley rats were castrated or sham operated at 16 weeks of age and fed either a standard or a high energy diet. Measured parameters were: food intake, body weight, fat distribution, energy expenditure, physical activity and blood/plasma parameters related to glucose and lipid metabolism. RESULTS: Castration led to an increase in the amount of subcutaneous fat, but did not result in any changes in the visceral fat. Fasting blood glucose levels were increased and free fatty acids concentration decreased in the castrated rats from 2 weeks after castration and throughout the study, whereas no significant differences between the groups were found in any of the other parameters measured. A high-energy diet did not change the response to castration in male Sprague-Dawley rats. CONCLUSION: Compared to humans rats respond differently to testosterone deficiency. Only few of the features typical for the human metabolic syndrome were observed in castrated male Sprague-Dawley rats. Therefore, we conclude that with the present experimental setup the castrated rat is not an optimal model for studies on the influence of testosterone deficiency on body fat distribution and the development of other central components of the metabolic syndrome.

Adipose Tissue↗

PubMed1996

Optimally functional fluorescein isothiocyanate-labelled fibrinogen for quantitative studies of binding to activated platelets and platelet aggregation.

Dynamic and quantitative studies of the binding of fibrinogen (Fg) to its receptor, GPIIb-IIIa, on activated platelets, leading to platelet aggregation, are best studied with fluorescently-labelled Fg by flow cytometry. Due to conflicting reports on the functionality of FITC-labelled Fg, we have developed a reproducible and 'mild' labelling of fibrinogen with FITC-celite at pH 7.4-8.5 for direct and dynamic studies of specific Fg binding to activated platelets evaluated for native platelet-rich plasma, for washed platelets, and for activated, fixed platelets. We have demonstrated the equivalence of FITC-labelled and unlabelled Fg for binding to activated GPIIb-IIIa receptors, and in the rate and extent of mediating platelet aggregation. We found that FITC-Fg labelled at pH > or = 9 had reduced to absent specific binding to activated platelets, whether using soluble FITC or FITC-celite. The FITC-labelled Fg must be diluted 3-fold with unlabelled Fg when evaluating maximal Fg binding to activated platelets in order to prevent autoquenching of the FITC-Fg which leads to underestimation of Fg levels. The dissociation constant (KD) of Fg on stable preparations of activated, fixed platelets, determined with FITC-Fg binding to platelets by flow cytometry, was in the range reported for 125I-labelled Fg, 70-255 nm with Bmax = 10000-25000 Fg per platelet (n = 20). The FITC-Fg was used to monitor Fg binding to activated platelets directly by plasma, as well as to evaluate platelet subpopulations which maximally bind Fg according to the concentration of ADP used as activator. It is expected that this 'mildly' labelled FITC-Fg will stimulate further studies of platelet activation directly in native anticoagulated blood/plasma, for both basic and clinical research.

Blood Platelets↗

PubMed2000

Reducing the risk of infection from plasma products: specific preventative strategies.

Collection and testing procedures of blood and plasma that are designed to exclude donations contaminated by viruses provide a solid foundation for the safety of all blood products. Plasma units may be collected from a selected donor population, contributing to the exclusion of individuals at risk of carrying infectious agents. Each blood/plasma unit is individually screened to exclude donations positive for a direct (e.g., viral antigen) or an indirect (e.g. anti-viral antibodies) viral marker. As infectious donations, if collected from donors in the testing window period, can still be introduced into manufacturing plasma pools, the production of pooled plasma products requires a specific approach that integrates additional viral reduction procedures. Prior to the large-pool processing, samples of each donation for fractionation are pooled ('mini-pool') and subjected to a nucleic acid amplification test (NAT) by, for example, the polymerase chain reaction (PCR) to detect viral genomes (in Europe: HCV RNA plasma pool testing is now mandatory). Any individual donation found PCR positive is discarded before the industrial pooling. The pool of eligible plasma donations (which may be 2000 litres or more) may be subjected to additional viral screening tests, and then undergoes a series of processing and purification steps that, for each product, comprise one or several reduction treatments to exclude HIV, HBV HCV and other viruses. Viral inactivation treatments most commonly used are solvent-detergent incubation and heat treatment in liquid phase (pasteurization). Nanofiltration (viral elimination by filtration), as well as specific forms of dry-heat treatments, have gained interest as additional viral reduction steps coupled with established methods. Viral reduction steps have specific advantages and limits that should be carefully balanced with the risks of loss of protein activity and enhancement of epitope immunogenicity. Due to the combination of these overlapping strategies, viral transmission events of HIV, HBV, and HCV by plasma products have become very rare. Nevertheless, the vulnerability of the plasma supply to new infectious agents requires continuous vigilance so that rational and appropriate scientific countermeasures against emerging infectious risks can be implemented promptly.

Biomarkers↗

PubMed1998

Indices of carbohydrate and lipid metabolism in vasopressin-replete and -deficient New Zealand genetically hypertensive rats.

Indices of carbohydrate and lipid metabolism were investigated in male New Zealand genetically hypertensive and normotensive rats. Cross-breeding of male rats of these strains with female Brattleboro diabetes insipidus rats also provided the opportunity to examine the metabolic impact of vasopressin and its deficiency in hypertensive and normotensive rats. Hypertensive and normotensive rats, with or without diabetes insipidus, were fasted for 24 h, exsanguinated and their blood/plasma analysed for various indices of carbohydrate and lipid metabolism. Whilst each group of rats maintained fasted normoglycemia, hypertensive rats, with or without vasopressin-deficiency, were hypoinsulinaemic relative to normotensive counterparts. Moreover, hypertensive or normotensive vasopressin-deficient rats were hypoinsulinaemic relative to vasopressin-replete counterparts. In vasopressin-replete rats, the apparently improved insulin sensitivity in hypertension was associated with significant falls in plasma glucagon, triglycerides and total cholesterol. Finally, normotensive vasopressin-deficient rats were hypoglucagonaemic relative to the vasopressin-replete group. These data demonstrate that independent of vasopressin status, hypertension in the New Zealand strain and the diabetes insipidus hybrid was associated with improved insulin sensitivity. However, endogenous vasopressin exercises an influential role in carbohydrate and lipid metabolism in normotensive rats.

Animals↗

PubMed2000

St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4.

BACKGROUND: St John's Wort (hypericum perforatum) is an herbal medicine that is frequently used for therapy of mild depression. Recently, St John's Wort was reported to substantially decrease blood/plasma concentrations and efficacy of cyclosporine (INN, ciclosporin), indinavir, and digoxin. In this study we investigated the mechanisms of these St John's Wort-induced drug interactions. METHODS AND RESULTS: In a preclinical study, the administration of St John's Wort extract to rats during 14 days resulted in a 3.8-fold increase of intestinal P-glycoprotein/Mdrl expression and in a 2.5-fold increase in hepatic CYP3A2 expression (Western blot analyses). In a clinical study, the administration of St John's Wort extract to 8 healthy male volunteers during 14 days resulted in an 18% decrease of digoxin exposure after a single digoxin dose (0.5 mg), in 1.4- and 1.5-fold increased expressions of duodenal P-glycoprotein/MDR1 and CYP3A4, respectively, and in a 1.4-fold increase in the functional activity of hepatic CYP3A4 (14C-erythromycin breath test). CONCLUSIONS: These results indicate direct inducing effects of St John's Wort on intestinal P-glycoprotein/MDR1 (in rats and humans), hepatic CYP3A2 (in rats), and intestinal and hepatic CYP3A4 (in humans). Therefore the results provide a mechanistic explanation for the previously observed drug interactions in patients and support the importance of intestinal P-glycoprotein/MDR1 in addition to intestinal and hepatic CYP3A4 for overall drug absorption and disposition in humans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds.

Several chronic bioassays have been conducted in multiple strains of mice in which various concentrations of arsenate or arsenite were administered in the drinking water without a tumorigenic effect. However, one study (Ng et al., 1999) reported a significant increase in tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. A physiologically based pharmacokinetic model for arsenic in the mouse has previously been developed (Gentry et al., 2004) to investigate potential differences in tissue dosimetry of arsenic species across various strains of mice. Initial results indicated no significant differences in blood, liver, or urine dosimetry in B6C3F1 and C57Bl/6 mice for acute or subchronic exposure. The current work was conducted to compare model-predicted estimates of tissue dosimetry to additional kinetic information from the (C57Bl/6 xCBA)F1 and TgAc mouse. The results from the current modeling indicate that the pharmacokinetic parameters derived based on information in the B6C3F1 mouse adequately describe the measured concentrations in the blood/plasma, liver, and urine of both the (C57Bl/6 x CBA)F1 and TgAc mouse, providing further support that the differences in response observed in the chronic bioassays are not related to strain-specific differences in pharmacokinetics. One significant finding was that no increases in skin or lung concentrations of arsenic species in the (C57Bl/6 x CBA)F1 strain were observed following administration of low concentrations (0.2 or 2 mg/U of arsenate in the drinking water, even though differences in response in the skin were reported. These data suggest that pharmacodynamic changes may be observed following exposure to arsenic compounds without an observable change in tissue dosimetry. These results provided further indirect support for the existence of inducible arsenic efflux in these tissues.

Administration, Oral↗

PubMed1991

Modelling approach for separating blood time-activity curves in positron emission tomographic studies.

A modelling approach is developed to generate the full time course of an injected radiotracer and its labelled metabolites in plasma/blood, based on measurements of the total radioactivities in withdrawn plasma/blood samples. A compartmental model is used to describe the conversion of an injected tracer to its metabolites in the body. The model equation is formulated with the total radioactivity concentration curve as the input function. The utility and characteristics of the approach in quantitative positron emission tomographic (PET) studies are shown with two examples. In the first example, using the tracer 6-[18F]fluoro-L-dopa (FDOPA), the approach is shown to derive the full time course of plasma FDOPA and its metabolites. In the second example of dynamic 15O oxygen PET, the approach is used to solve a deconvolution problem to give separated time-activity curves of 15O oxygen and 15O water in blood. The modelling approach improves the separation of blood/plasma time-activity curves and leads to better quantitative interpretation of PET results.

Dihydroxyphenylalanine↗

PubMed2006

The increase of breath ammonia induced by niacin ingestion quantified by selected ion flow tube mass spectrometry.

The ingestion of relatively large doses of the vitamin niacin by healthy volunteers results in a reddening of the skin, a skin 'flush'. Thus, we have carried out a study of the breath metabolites of two healthy volunteers following (i) the ingestion of 200 mg of immediate-release niacin, (ii) as (i) but preceded by the ingestion of 325 mg of aspirin that diminishes the skin 'flush', (iii) ingestion of 500 mg of slow-release niacin. On-line breath analysis was carried out using selected ion flow tube mass spectrometry, SIFT-MS. The interesting new observation is that the breath ammonia levels of both volunteers clearly increased following (i) and (ii), and an obvious skin flush did occur following (i) but not following (ii). The slow-release niacin (iii) did not result in a flush and the breath ammonia levels increased more slowly and did not reach the higher levels produced by (i) and (ii). The results of these experiments demonstrate that breath ammonia levels are dependent on the blood/plasma levels of niacin, but are not directly related to the flushing phenomenon, and that the observed increases in blood/breath ammonia levels are consistent with current knowledge of the metabolic pathways of niacin. The parallel measurements of breath isoprene are presented, which demonstrate the quality of breath analyses that can be achieved using SIFT-MS.

Administration, Oral↗

PubMed2001

Prevalence of HIV infection among former commercial plasma donors in rural eastern China.

BACKGROUND: Sporadic reports of HIV-1 infection among commercial plasma donors in China between 1994 and 1995. OBJECTIVES: (1) To determine the prevalence of HIV infection among repeat plasma donors; (2) to identify factors associated with HIV infection; and (3) to describe characteristics associated with secondary transmission. METHODS: Plasma/blood donors who had a history of donating plasma/blood before March 1, 1995, their spouses, and their children under 5 years were recruited for a cross-sectional study. A questionnaire and an HIV test were collected anonymously. Information collected included demographic characteristics, sexual behaviour, recreational drug use and history of medical care and blood/plasma donation. HIV antibody was identified by the Hema-Strip rapid test and confirmed by Western blot. The prevalence of HIV infection was calculated and risk factors associated with infection determined by univariate analyses followed by multivariate modelling. RESULTS: A total of 1517 individuals were interviewed and tested, of whom 1043 adults admitted to donating plasma. The prevalence of HIV infection among plasma donors was 12.5% and among their non-donor spouses was 2.1%. Prevalence was inversely related to educational level and was higher in married participants, but was not associated with medical care, drug abuse or multiple sexual partners. A higher frequency of plasma donation was directly associated with a higher risk of HIV infection. Multivariate analyses demonstrated that being HIV-positive was associated with being 30 to 49 years old [odds ratio (OR) = 1.9], donating both plasma and blood (OR = 2.5), and the frequency of plasma donation (OR = 14 for >10 donations per month). CONCLUSION: The study demonstrated that the prevalence of HIV infection in the commercial plasma donor population was alarmingly high. Many married individuals and those getting married in the future will transmit the virus to their spouses and future children. Plasma donors need to be alerted to the risk of being infected with HIV and of transmitting HIV to their families and others. Other countries can benefit from the experience of China in reducing the risk of HIV transmission from plasma donating.

AIDS Serodiagnosis↗

PubMedDate not supplied

Quantitative high-performance liquid chromatography determination of ICI 125,211 in plasma.

A rapid, specific and quantitative high-performance liquid chromatography assay procedure is described for the determination of ICI 125, 211, (I), a guanidino-thiazole H2-receptor antagonist, in small samples of animal plasma. A 0.2 mL aliquot of plasma is extracted at pH 9 with ethyl acetate. After reconstitution in mobile phase, the sample is run on a silica column using ultraviolet detection at 280 nm. The procedure utilizes ICI 125, 253, (II), an analogous compound as the internal standard. The assay is linear (r2 = 0.99) and the recovery is 97.6 +/- 6.38% over a concentration range of 0.050-5.00 microgram/mL. Detection of levels as low as 0.025 microgram/mL has been documented in some animal study samples. Typical day-to-day precision is 3-9%, relative, for triplicate determinations of four concentrations in the 0.050-0.500 microgram/mL concentration range. Compound (I) is stable in whole blood for at least two hours at room temperature. Plasma concentrations remain constant for at least 48 hours at room temperature and six months at -5 degrees C. The whole blood/plasma ratio averages 0.97 +/- .073 for dog blood (N = 5). Pharmacokinetic data gathered for two dogs dosed orally with an HPMC-TWEEN 80 suspension of (I) at 40 mg/kg gave elimination half-life values of 4.3 and 7.4 hours. The specificity of the HPLC procedure has been confirmed by mass spectrometry.

Animals↗