Bioaccessible arsenic in soil of thermal areas of Viterbo, Central Italy: implications for human health risk.

Thermal waters near the city of Viterbo (Central Italy) are known to show high As contents (up to 600 µg/l). Travertine is precipitated by these waters, forming extended plateau. In this study, we determine the As content, speciation and bioaccessibility in soil and travertine samples collected near a recreational area highly frequented by local inhabitants and tourists to investigate the risk of As exposure through accidental ingestion of soil particles. (Pseudo)total contents in the studied soils range from 17 to 528 mg/kg, being higher in soil developed on a travertine substrate (197 ± 127 mg/kg) than on volcanic rocks (37 ± 13 mg/kg). In travertines, most As is bound to the carbonatic fraction, whereas in soil the semimetal is mostly associated with the oxide and residual fractions. Accordingly, bioaccessibility (defined here by the simplified bioaccessibility extraction test, SBET; Oomen et al., 2002.) is maximum (up to 139 mg/kg) for soil developed on a travertine substrate, indicating a control of calcite dissolution on As bioaccessibility. On the other hand, risk analysis suggests a moderate carcinogenic risk associated with accidental soil ingestion, while dermal contact is negligible. By contrast, ingestion of thermal water implies a higher carcinogenic and systemic health risk.

Interplay of HD-Zip II and III transcription factors in auxin-regulated plant development.

The homeodomain-leucine zipper (HD-Zip) class of transcription factors is unique to plants. HD-Zip proteins bind to DNA exclusively as dimers recognizing dyad symmetric sequences and act as positive or negative regulators of gene expression. On the basis of sequence homology in the HD-Zip DNA-binding domain, HD-Zip proteins have been grouped into four families (HD-Zip I-IV). Each HD-Zip family can be further divided into subfamilies containing paralogous genes that have arisen through genome duplication. Remarkably, all the members of the HD-Zip IIγ and -δ clades are regulated by light quality changes that induce in the majority of the angiosperms the shade-avoidance response, a process regulated at multiple levels by auxin. Intriguingly, it has recently emerged that, apart from their function in shade avoidance, the HD-Zip IIγ and -δ transcription factors control several auxin-regulated developmental processes, including apical embryo patterning, lateral organ polarity, and gynoecium development, in a white-light environment. This review presents recent advances in our understanding of HD-Zip II protein function in plant development, with particular emphasis on the impact of loss-of-function HD-Zip II mutations on auxin distribution and response. The review also describes evidence demonstrating that HD-Zip IIγ and -δ genes are directly and positively regulated by HD-Zip III transcription factors, primary determinants of apical shoot development, known to control the expression of several auxin biosynthesis, transport, and response genes. Finally, the interplay between HD-Zip II and III transcription factors in embryo apical patterning and organ polarity is discussed.

Assessment of the Efficiency of Consolidation Treatment through Injections of Expanding Resins by Geotechnical Tests and 3D Electrical Resistivity Tomography.

The design and execution of consolidation treatment of settled foundations by means of injection of polyurethane expanding resins require a proper investigation of the state of the foundation soil, in order to better identify anomalies responsible for the instability. To monitor the injection process, a procedure has been developed, which involves, in combination with traditional geotechnical tests, the application of a noninvasive, geophysical technique based on the electrical resistivity, which is strongly sensitive to presence of water or voids. Three-dimensional electrical resistivity tomography is a useful tool to produce effective 3D images of the foundation soils before, during, and after the injections. The achieved information allows designing the consolidation scheme and monitoring its effects on the treated volumes in real time. To better understand the complex processes induced by the treatment and to learn how variations of resistivity accompany increase of stiffness, an experiment was carried out in a full-scale test site. Injections of polyurethane expanding resin were performed as in real worksite conditions. Results confirm that the experimented approach by means of 3D resistivity imaging allows a reliable procedure of consolidation, and geotechnical tests demonstrate the increase of mechanical stiffness.

Hyperbilirubinemic stain: location and extent in dental tissues.

OBJECTIVE: The purpose of the present manuscript is to describe the location and extent of hyperbilirubinemic stain in a primary molar of a 3-year-old who was diagnosed with cystic fibrosis shortly after birth, subsequently developed liver disease and hyperbilirubinemia, and received a liver transplant at age 10-months. STUDY DESIGN: Clinical and histological assessments were performed to evaluate the location and extent of hyperbilirubinemic stain in an extracted primary molar. RESULTS: The clinical image, and macroscopic and microscopic histological examinations of a primary molar showed hyperbilirubinemic staining of enamel and of the coronal dentin that developed between birth and when the liver transplant took place, irregular dentin tubules, and an irregular cementum-dentinal junction. CONCLUSIONS: The findings of the present manuscript indicate that hyperbilirubinemc staining of primary teeth affects dental hard tissues at the time of their calcification, and the clinical picture of the stain may be related to stained enamel and/or dentin, and underlying stained dentin visible through translucent unstained enamel.

Purification and characterization of eight class 5 outer membrane protein variants from a clone of Neisseria meningitidis serogroup A.

Methods published for the purification of P.II proteins from Neisseria gonorrhoea have been modified to allow the purification of class 5 proteins from Neisseria meningitidis serogroup A bacteria. The five class 5 protein electrophoretic variants detected within an epidemic in the Gambia (a, b, c, d, and e) and three other variants (f, g, and h) found within other isolates of the same clone in West Africa have been purified with yields of 6-28 mg. The NH2-terminal amino acid sequence for variant c differs from those of the other class 5 proteins, whereas the latter are very similar to the sequence predicted for two class 5 proteins from DNA analyses of serogroup C meningococci and determined for 8 P.II proteins from gonococci. Numerous other regulatory, chemical, and serological differences were found between the c protein and the other class 5 proteins such that we recommend that the class 5 proteins be subdivided into two subclasses. mAbs have been isolated that distinguish between these two protein subclasses and Western blotting with these antibodies enabled us to conclude that both protein subclasses were found in bacteria isolated from different epidemics and pandemics of the last 50 yr.

A Survey of Dog Owners' Attitudes toward Treats.

Commercially available dog treats have become very popular and a common part of the pet's diet, yet very little is known about peoples' opinions and feeding habits; therefore, a survey was shared on a popular social network.Most of the self-selected interviewed owners (n = 1833, 83%) use treats regularly, mainly to reward their dog's behavior or during training-sports activities. Owners usually buy several types of treats, of which biscuits and dental care sticks are the most common, and usually hand out one to five pieces to their dogs every day. Most owners read the labels of the treats to seek the ingredients list and the claimed health benefits; contrarily, many owners look for non-nutritional values, such as flavor (n = 321, 18%), brand (n = 72, 4%) or shape (n = 46, 3%). Seventy-five percent of the owners (n = 1369) follow the feeding instructions provided by the producers on the label.Treat feeding is a common practice among dog owners and there is great variability among regimens (e.g., types and quantities provided). Understanding the owner's attitudes could help veterinarians educate them to manage treats in the dog's diet.

A 200 km-long mercury contamination of the Paglia and Tiber floodplain: Monitoring results and implications for environmental management.

This paper reports the results of a joint project carried out by three regional environmental agencies of Italy to evaluate long-range mercury (Hg) transport from the abandoned Mt. Amiata Hg district in southern Tuscany (the third largest worldwide site for Hg production) to the fluvial ecosystems of the Paglia and Tiber rivers. Most of the work focused on stream sediments, surface waters and soils. A preliminary survey of Hg0 content in air was also conducted. Data obtained by public health authorities on Hg in vegetables and fish were also included. The highest Hg concentrations (up to thousands of µg/g Hg) were observed in stream sediments and soils directly impacted by Hg mine runoff. Although progressive Hg dilution was observed from north to south along the river, sediments and soils show anomalous Hg levels for over 200 km downstream of Mt. Amiata, testifying to an extreme case of long-range Hg contamination. A pervasive redistribution of Hg is observed in all sediment compartments. Presumably, the width of the impacted fluvial corridor corresponds to the entire alluvial plains of the rivers. The floodplains can be considered new sources for downstream Hg redistribution, especially during large flood events. On the other hand, results from water, air, and vegetable sampling indicate low potential for human exposure to Hg. The extent and distribution of the contamination make remediation not viable. Therefore, people and human activities must coexist with such an anomaly. On the technical side, the most urgent action to be taken is a better definition of the exact extent of the contaminated area. On the management side, it is necessary to identify which public institution(s) can best deal with such a widespread phenomenon. According to the precautionary principle, the impact of the contamination on human activities in the affected areas should be considered.

Subclinical visual field alterations are commonly present in patients with Graves' Orbitopathy and are mainly related to the clinical activity of the disease.

The present study was aimed to investigate optic nerve involvement by computerized perimetry in 40 (29 women, 11 men) consecutive GO patients not showing definite dysthyroid optic neuropathy (DON). All patients presenting visual acuity defects, pallor or swelling of the optic nerve, concomitant eye disease, evidence of apical crowding or optic nerve stretching at either MRI or CT imaging were excluded. Normal perimetry occurred in 7 patients (17.5%), 5 patients (12.5%) had "indeterminate" results and 28 patients (70%) presented abnormal perimetry. Particularly, 7 isolated paracentral, 5 pericentral and 16 combined peri and paracentral scotomas were found. On the contrary, 15/20 patients in the group without GO had normal perimetry, isolated scotomas were found in 5 cases (1 pericentral and 4 paracentral) and no case of combined scotoma occurred. The difference between the 2 groups was statistically significant (x2 = 9.17; p = 0.025). Overall, the sensitivity resulted 70%, the specificity 75% and the positive predictive value 84.8%. In patients with GO, the proportion of visual field alterations was significantly increased for Clinical Activity Score > or = 3 (p = 0.0005), while no relationship occurred with proptosis degree (p = 0.115). In conclusion, a great proportion of GO patients without clinically evident DON presents visual field defects, mainly related to GO activity.

Is sonographic surveillance of polytetrafluoroethylene-covered transjugular intrahepatic portosystemic shunts (TIPS) necessary? A single centre experience comparing both types of stents.

AIM: To investigate whether sonographic (US) surveillance of polytetrafluoroethylene covered transjugular intrahepatic portosystemic shunts (TIPS) is necessary. MATERIALS AND METHODS: We identified 128 patients who underwent TIPS for complications of portal hypertension between January 2001 and December 2005 at a large tertiary centre. Procedural data were retrospectively analysed. US surveillance of the TIPS was performed at baseline with scheduled follow-up or whenever shunt dysfunction was suspected. Clinical and radiology reports were compared to assess US surveillance of the TIPS. RESULTS: Four hundred and twenty-six US studies were performed, with a median of three per patient (range 1-5). The median follow-up period was 378 days (range 1-1749 days). Twenty-three patients (18%) had baseline US studies performed only whereas 105 (82%) also had follow-up studies. Forty-one (32%) of 128 patients [32 (78%) Wallstent, nine (22%) Viatorr] had Doppler ultrasound abnormalities noted. Venography was performed in all 41 patients. Abnormal venography and elevated hepatic venous pressure gradient (HVPG) was seen in 34 (82.9%) of the 41 patients [29 (85.3%) Wallstent, five (14.7%) Viatorr]. Among the 34 patients, 17 (50%) [13 (76.5%) Wallstent, four (23.5%) Viatorr] had venographic abnormalities noted at the hepatic venous end accompanied by increased HVPG. All four of the Viatorr patients had minor narrowing at the hepatic venous end and HVPG measurements that ranged 3-4 mm Hg above 12 mm Hg. CONCLUSION: Considering the improved patency of covered stents in TIPS, US surveillance may be superfluous after the baseline study.

Collagenase clostridium histolyticum for the treatment of Peyronie's disease: a prospective Italian multicentric study.

Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. However, only few monocentric studies are available in the current literature and this is the first national multicentric study focusing on this new treatment. In five Italian centres, 135 patients have completed the treatment with three injections of CCH using Ralph's shortened modified protocol. The protocol consisted of three intralesional injections of CCH (0.9 mg) given at 4-weekly intervals in addiction to a combination of home modelling, stretching and a vacuum device on a daily basis. An improvement in the angle of curvature was recorded in 128/135 patients (94.8%) by a mean (range) of 19.1 (0-40)° or 42.9 (0-67)% from baseline (p < 0.001). There was also a statistically significant improvement in all IIEF and PDQ questionnaires subdomains (p < 0.001 in all subdomains). This prospective multicentric study confirms that the three-injection protocol is effective enough to achieve a good result and to minimize the cost of the treatment.

Pharmacokinetics of lamivudine, zidovudine, and nevirapine administered as a fixed-dose combination formulation versus coadministration of the individual products.

The pharmacokinetics of 150 mg lamivudine, 300 mg zidovudine, and 200 mg nevirapine were assessed following single oral administration of a fixed-dose combination tablet and coadministration of the separate innovator products in healthy male subjects (n = 64) under fasting conditions in an open-label, randomized, 2-way crossover study. Multiple blood samples were collected up to 72 hours and plasma concentrations of antiretrovirals were assayed using liquid chromatography/tandem mass spectrometry methods. Pharmacokinetic parameters were calculated using noncompartmental methods, and bioequivalence was assessed using an analysis of variance model. The ratio of the least squares mean (fixed-dose combination to individual products) and 90% confidence intervals of AUC(0-t), AUC(0-infinity), and C(max) for lamivudine, zidovudine, and nevirapine were all within 80.0% to 125.0%, suggesting a similar rate and extent of antiretroviral exposure in the bloodstream. Mean oral clearance (CL/F) values of lamivudine, zidovudine, and nevirapine for the fixed-dose combination were 23.7, 127, and 1.65 L/h, respectively. The fixed-dose combination and individual products were equally safe and well tolerated, with only a few subjects experiencing drug-related adverse events. The current fixed-dose combination of lamivudine, zidovudine, and nevirapine is expected to provide a similar efficacy/safety profile as coadministration of the individual products, a better adherence to treatment, and considerable cost savings in the treatment of HIV.

Structure and developmental regulation of a wheat gene encoding the major chlorophyll a/b-binding polypeptide.

A genomic clone for a major chlorophyll a/b-binding polypeptide of the light-harvesting complex has been sequenced from wheat. This gene, whAB1.6, encodes a 70-nucleotide 5'-nontranslated spacer, a 34-amino-acid NH2-terminal extension, i.e., the transit peptide, and a mature coding protein of 232 amino acid residues. The exact molecular weight of the precursor polypeptide is 28,560. The transit peptide is basic and is rich in serines. No intervening sequences are found in this gene. The transcription start site of the whAB1.6 gene occurs at AAAC as determined by S1 nuclease analysis. Putative regulatory sequences occur upstream of the gene at -25 (TTTAAATA) and at -72 (CCAACCA). Northern blots show a single RNA species estimated to be 1,100 nucleotides. Heterogeneity of the RNA population is demonstrated in S1 nuclease analyses with a 5'-end-labeled fragment that extends 191 nucleotides into the mature protein coding sequence. At least seven different transcripts can be recognized. The highest levels of RNA transcribed from the whAB1.6 gene are found in the basal segments of the wheat leaf, whereas other chlorophyll a/b-binding transcripts in the cell show a different pattern of abundance. As a control, we show that roots do not contain chlorophyll a/b-binding RNA. The most abundant RNA species shows an interrupted homology with the whAB1.6 gene at the start of the mature protein coding sequence; another species shows homology beginning at the start of the transit peptide and does not include the nontranslated region. Chlorophyll a/b-binding polypeptides accumulate toward the tip of the leaf as shown by Western blot analysis of total thylakoid proteins.

Molecular cloning of a Neurospora crassa carotenoid biosynthetic gene (albino-3) regulated by blue light and the products of the white collar genes.

The albino-3 (al-3) gene of Neurospora crassa, which probably encodes the carotenoid biosynthetic enzyme geranylgeranyl pyrophosphate synthetase, was cloned. The N. crassa triple mutant al-3 qa-2 aro-9 was transformed to qa-2+ with mixtures of plasmids bearing N. crassa DNA inserts, and the transformants were screened for the al-3+ phenotype. One al-3+ qa-2+ transformant (AL3-1) was examined in detail and shown to contain intact vector sequences integrated into the N. crassa genome. The vector and some flanking sequences were recovered from AL3-1 after restriction, ligation, and selection of chloramphenicol-resistant transformants of Escherichia coli. The flanking sequences were subsequently used to detect the al-3-containing plasmid in the mixture of about 1,800 plasmids. Restriction fragment length polymorphism mapping was carried out to confirm the identity of the cloned fragment. The level of the al-3 mRNA was shown to be increased 15-fold in light-induced (compared with that in dark-grown) wild-type mycelia. The light-dependent increase in al-3 mRNA levels was not observed in presumed regulatory mutant (white collar) strains.

Prulifloxacin versus levofloxacin in the treatment of chronic bacterial prostatitis: a prospective, randomized, double-blind trial.

Ninety-six patients with chronic bacterial prostatitis (CBP) and evidence of infection were randomized to receive a 4-week oral course of either prulifloxacin (a new fluoroquinolone) 600 mg or levofloxacin 500 mg once daily. They were evaluated with the Meares-Stamey test and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at baseline and one week after therapy completion. Patients with microbiological eradication were evaluated again with the Meares-Stamey test 6 months after therapy completion. The microbiological eradication rate was 72.73% for prulifloxacin and 71.11% for levofloxacin (p=0.86) and the reduction in the NIH-CPSI was 10.75 and 10.73, respectively (p=0.98). Safety was comparable, with 18.18% adverse events for prulifloxacin and 22.22% for levofloxacin (p=0.79). Thus, a 4-week course of prulifloxacin 600 mg once daily is at least as effective and safe as levofloxacin 500 mg once daily in the treatment of CBP.

All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database.

BACKGROUND: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. AIM: To assess efficacy of all-oral HCV therapy in advanced liver disease. METHODS: Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. RESULTS: Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. CONCLUSIONS: All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.

Epistaxis after PDE-5 inhibitors misuse.

A 32-year-old male presented to our department for recurrent epistaxis during sexual intercourses. The patient controlled the bleeding each time with sponge packs and gauzes. During the consultation, he volunteered that the trigger for the epistaxis appeared to have been misuse of phosphodiesterase (PDE)-5 inhibitors, Viagra and Cialis. This first report of epistaxis after PDE-5 inhibitors in a young patient underline the possibility that in the next years the number of similar cases might increase due to the diffusion of PDE-5 inhibitor misuse in recreational settings.

Comparative bioavailability of a generic capsule formulation of the reverse transcriptase inhibitor efavirenz and the innovator product.

OBJECTIVE: Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been used successfully for more than a decade to treat human immunodeficiency virus (HIV) infection. The objective of the current study was to determine the bioequivalence between a generic capsule formulation of efavirenz and the innovator product. MATERIAL AND METHODS: A total of 41 healthy subjects (34 males and 8 females) received a single 200 mg oral dose of efavirenz as the generic (Ranbaxy-Efavirenz, Ranbaxy Laboratories Ltd.) and innovator (Sustiva, Bristol-Myers Squibb) capsule formulations under fasting conditions in a randomized, 2-way crossover study. Multiple blood samples were collected over 72 hours and plasma concentrations of efavirenz were assayed using an LC/MS/MS method. Pharmacokinetic (PK) parameters were calculated using non-compartmental methods. RESULTS: Plasma concentrations of efavirenz peaked within 2.5 hours and then declined in a multi-exponential manner for both formulations. At 72 hours post dose, all plasma concentrations of efavirenz were above the LOQ of the assay (10 ng/ml). Mean area under the curve from 0 - 72 hours (AUC0-72) and maximum plasma concentrations (Cmax) of efavirenz for the generic capsule formulation were 22,840 ng x h/ml and 1,199 ng/ml, respectively. Ratios and 90% confidence intervals of PK parameters between the two formulations were within 80.0 - 125.0%, suggesting that the two capsule formulations resulted in similar rate and extent of bioavailability under fasting conditions. Adverse events were similar in nature and frequency for the two formulations. CONCLUSIONS: Based on the above results, the generic capsule formulation of efavirenz developed by Ranbaxy should be as effective as the innovator product.

Comparative bioavailability study of zidovudine administered as two different tablet formulations in healthy adult subjects.

AIM: Zidovudine is a synthetic nucleoside analogue of thymidine with activity against the human immunodeficiency virus type 1 (HIV-1). In patients with HIV infections or the acquired immunodeficiency syndrome (AIDS), zidovudine is a first-line therapy that was shown to reduce morbidity, mortality, and hospitalization. A generic formulation of zidovudine offers the possibility of considerable savings to HIV/AIDS patients in developed and Third World countries. The objective of the current study was to characterize the pharmacokinetic and safety profiles of zidovudine administered as a generic tablet formulation relative to the innovator product. VOLUNTEERS AND METHODS: A total of 68 healthy adult volunteers received a 300 mg oral dose of zidovudine as the generic formulation (AVIRO-Z 300 mg tablet, Ranbaxy Laboratories Limited) and as the innovator product (Retrovir tablet, GlaxoSmithKline) in a randomized, 2-way crossover study. Multiple blood samples were collected over 12 hours and plasma concentrations of zidovudine were assayed using an LC/MS/MS method with an analytical range of 5.00 to 2,000 ng/ml. Pharmacokinetic parameters were calculated using non-compartmental methods. RESULTS: Mean plasma concentrations of zidovudine declined in a mono-exponential manner, with mean concentration values falling below the limit of quantitation 12 hours after administration of both formulations. Mean area under the curve from time 0 to the last measurable concentration (AUC(0-t)), mean area under the curve from time 0 to infinity (AUC(0-infinity)) and peak plasma concentrations (C(max)) of zidovudine for the generic tablet formulation (2,220.6 ng x h/ml, 2,236.0 ng x h/ml and 1,087.9 ng/ml, respectively) were very similar to those observed for the innovator product (2,139.7 ng x h/ml, 2,158.6 ng x h/ml and 1,066.5 ng/ml, respectively). Ratios of least-squares means and 90% confidence intervals of AUC(0-t) AUC(0-infinity) and C(max) between the 2 formulations were within 80-125%, suggesting that the two tablet formulations displayed similar rate and extent of bioavailability. The oral clearance (CL/F) of zidovudine for the generic and innovator formulations were 2.11 1/h/kg and 2.16 1/h/kg, respectively. For the two formulations, adverse events were similar in nature and frequency. CONCLUSION: Since the two formulations displayed similar in vivo delivery rate of zidovudine in the bloodstream, the generic tablet formulation of zidovudine developed by Ranbaxy should be equally effective as the innovator product and is expected to produce considerable cost-savings in AIDS patients worldwide.

Bioequivalence of abacavir generic and innovator formulations under fasting and fed conditions.

OBJECTIVE: Abacavir sulfate is a synthetic carbocyclic nucleoside analogue indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. The objective of the current study was to determine the bioequivalence between a generic formulation of abacavir and the innovator product. MATERIAL AND METHODS: A total of 80 subjects were randomly assigned to receive a single 300 mg oral dose of abacavir sulfate as the generic (Ranbaxy-Abacavir, Ranbaxy Laboratories Ltd., equivalent to 300 mg of abacavir) and innovator (Ziagen, GlaxoSmithKline) tablet formulations in 2-way crossover studies performed under fasting (n=40) and fed (n=40) conditions. Multiple blood samples were collected over 14 hours and plasma concentrations of abacavir were assayed using an LC/MS/MS method with a limit of quantitation of 25.0 ng/ml. Pharmacokinetic (PK) parameters were calculated using noncompartmental methods. RESULTS: Under fasting conditions, geometric mean area under the curve from time 0 to the last measurable concentration (AUC(0-t)), area under the curve extrapolated to infinity (AUC(0-infinity) and maximum plasma concentrations (Cmax) of abacavir for the generic (5565 ng x h/ml, 5668 ng x h/ml and 2526 ng/ml, respectively) and innovator (5675 ng x h/ml, 5770 ng x h/ml and 2528 ng/ml, respectively) products were very similar. Under fed conditions, mean values of AUC(0-t) AUC(0-infinity) and Cmax for the generic (4487 ng x h/ml, 4571 ng x h/ml and 1841 ng/ml, respectively) and innovator (4574 ng x h/ml, 4654 ng x h/ml and 1781 ng/ml, respectively) formulations were also very similar. Ratios of LSM and 90% confidence intervals of PK parameters between the 2 formulations were within 80.0 - 125.0% under fasting and fed conditions, suggesting that the 2 tablet formulations resulted in similar rate and extent of bioavailability. Adverse events for the generic and innovator products were similar in nature and frequency in the fasting and fed studies. CONCLUSIONS Based on the above results, the generic tablet formulation of abacavir developed by Ranbaxy should be equally effective as the innovator product.