Mechanism-Based QSAR Modeling of Skin Sensitization.

Many chemicals can induce skin sensitization, and there is a pressing need for non-animal methods to give a quantitative indication of potency. Using two large published data sets of skin sensitizers, we have allocated each sensitizing chemical to one of 10 mechanistic categories and then developed good QSAR models for the seven categories that have a sufficient number of chemicals to allow modeling. Both internal and external validation checks showed that each model had good predictivity.

Extraction and characterization of natural lignocellulosic fibres from Typha angustata grass.

In recent years, efforts have been made to reduce deforestation to conserve the ecosystem. In the current scenario, agro-cultivated products are used instead of wood for engineering applications. Thus, natural lignocellulosic fibres are used as a reinforcing material and have been extremely attractive to industries and the scientific community during the past few decades. This study aimed to examine the use of natural fibres extracted from Typha angustata grass as reinforcement in polymer matrix composites. The density of the fibres was 1.015 g/cc. Chemical analysis confirmed that T. angustata fibres (TAFs) have a cellulose content of 73.54 wt%, a hemicellulose content of 10.11 wt%, a lignin content of 6.23 wt% and a wax content of 0.23 wt%. The crystallinity index (65.16 %) and crystalline size (6.40 nm) were identified by X-ray diffraction (XRD) analysis. The presence of functional groups in the TAFs was examined by employing Fourier-transform infrared spectroscopy (FTIR). The presence of cellulose at peak intensities of C2, C3 and C5 in the TAFs was confirmed using 13C nuclear magnetic resonance (NMR) spectroscopy. The single fibre tensile test revealed that the tensile strength was 665 ± 7 MPa and Young's modulus was 27.45 ± 3.46 GPa. The thermal stability of the TAFs was examined by thermogravimetric analysis (TGA), and the prominent peak was observed at 298.48 °C, with a kinetic activation energy of 67.99 kJ/mol. The surface roughness of the fibres was analysed by atomic force microscopy (AFM) with an accuracy of 1 nm. The above-mentioned outcomes indicated that the TAFs have desirable properties that are comparable to existing natural fibres and suggested to be utilised as the possible reinforcement to fabricate the fibre-reinforced polymer matrix composites.

Characterization of natural cellulosic fibers from Nendran Banana Peduncle plants.

The objective of this work is to explore the natural cellulosic fibers extracted from Nendran Banana Peduncle plants. This is the first time, the tests are carried out in the Nendran Banana Peduncle Fiber (NBPF) to measure the properties of the chemical, physical, mechanical, thermal (TGA/DTG), X-ray Diffraction (XRD) analysis, Fourier-transform Infrared spectroscopy(FT-IR), Nuclear Magnetic Resonance (NMR) analysis and Atomic Force Microscopy (AFM) furnished in this work. The Weibull distribution analysis was adopted for the analysis of diameter, tensile strength and Young's modulus of the fiber. The XRD analysis for the NBPF shows that the crystallinity index of 53.3%and crystallinity size of 4.72 nm. Thermogravimetric analysis depicted that NBPF can withstand thermally up to 356 °C. FT-IR results proved the existence of different chemical compositions and their corresponding functional groups. AFM analysis revealed the surface of the fiber found as rough. From the results, it is concluded that NBPF utilized as a polymer matrix composite for manufacturing light load automotive components and construction equipment.

UNCERTAINTY EVALUATION IN DOSE ASSESSMENT DUE TO SPATIAL DISTRIBUTION OF NORM IN BEACH SANDS OF SOUTHEAST COAST OF INDIA: A PROBABILISTIC APPROACH.

A study on radionuclide distribution along coastal stretch in high background areas is constantly attracted to many researchers around the world. In the present study, the concentration of radionuclides in beach sands along the southeast coastal region of India has been studied in detail. Concentration of radionuclides is measured using gamma spectrometry at 148 pre-determined locations. It is found that 238U and 232Th concentrations are varying in the range from 3 (BDL) to 298.9 and 1150.2 Bq kg-1, respectively. Concentration of 40K in beach sand varied from 11 to 1743.4 Bq kg-1. The measured activity levels of radionuclides were compared with earlier studies carried out by various researchers in the same region under study. The related radiological parameters of interest were also determined and compared with the internationally recommended values. With an increase in emphasis on quality in dose assessment methods, dose to human population living in the vicinity requires uncertainty evaluation, which is carried out by taking into account variation in the activity values. This study would serve as a baseline radiological mapping for the southeast coast region of India for environmental impact assessment prior to plan of nuclear facility in the future.

A REVIEW ON 210Po AND 210Pb IN INDIAN SEAFOOD AND DOSE TO CONSUMERS.

India is the second largest seafood producer in the world marketing more than 7000 edible species. In this regard, commendable studies have been conducted since the 1970s by different research groups and more data are reported. In this work, all the studies on 210Po and 210Pb measurements in abiotic and biotic components of India have been combined and reviewed. The concentrations of 210Po and 210Pb are estimated by radiochemical separation followed by alpha counting. Grain size, season, Tsunami waves and place of sampling have a decisive bearing on 210Po and 210Pb concentration in abiotic components. Plankton shows a higher Kd factor (104) compared to seaweeds and sea grass (103). Pond ecosystems recorded the highest Kd factor (4·3 × 104) compared to other freshwater and marine ecosystems. Bioaccumulation of 210Po and 210Pb varies with respect to variety of seafood. The committed effective dose (CED) calculated for shellfish species maintained a higher range of 2.5 × 10-2 mSv/y to 9.8 × 10-1 mSv/y and for fish species fluctuated from 3.8 × 10-4 mSv/y to 2.0 × 10-1 mSv/y. The studies conducted so far are scattered, and need to be gathered for future reference and planning (i.e. There is not much information available for Kerala, Karnataka, Maharashtra, Gujarat, Andhra, West Bengal and Odessa coast). Therefore, it is strongly recommended that further and more complete research is undertaken to study the bioaccumulation of 210Po and 210Pb from seafood. Overall, the present review concludes that Indian seafood is radiologically safe.

Utilization pattern and cost of sedation, analgesia and neuromuscular blockade in a multidisciplinary intensive care unit.

OBJECTIVES: To study the utilization pattern and the cost of sedatives, analgesics and neuromuscular blocking agents in a multidisciplinary intensive care unit (ICU). METHODS: A prospective observational study was conducted in the ICU of the Eric Williams Medical Sciences Complex, Trinidad and Tobago, for a period of twelve weeks. All patients admitted to the ICU were enrolled. No interventions were done. Data collected included demographics, diagnoses on admission, length of stay in the ICU, status of mechanical ventilation, patient outcome, quantity of sedatives, analgesics and neuromuscular blocking agents used in every patient and their cost. RESULTS: There were 333 patient-days encountered from 34 patients studied. Midazolam, fentanyl and cisatracurium were the most commonly used sedative, opioid and neuromuscular blocking agents respectively. The total cost of drugs used for sedation, analgesia and neuromuscular blockade was approximately US$ 19,600 per annum. Cost for this treatment alone accounted for more than 50% of the total ICU drug costs. The costs were significantly higher in patients who stayed more than two weeks in the ICU when compared to those who stayed less than two weeks (p < 0.001). CONCLUSIONS: The study highlights the utilization pattern and financial burden of sedation, analgesia and neuromuscular blockade in the delivery of critical care.

DISTRIBUTION AND BIOACCUMULATION OF 210Po AND 210Pb IN ABIOTIC AND BIOTIC COMPONENTS OF THE BAY OF BENGAL.

Marine environment is enriched source of heavy minerals associated with radionuclides which are largely responsible for human exposure to radiation. Bay of Bengal is one among the important marine ecosystems in the world because of its high biodiversity. The aim of this work was to generate a comprehensive data on distribution and bioaccumulation of 210Po and 210Pb in marine environment of the Bay of Bengal. For this water and sand samples (10 stations), shellfishes (21 species) and fishes (43 species) were collected and the concentrations of 210Po and 210Pb were measured by radiochemical separation followed by alpha counting method using ZnS(Ag) detector. 210Pb concentration in the marine water (mean: 7.6 ± 3.31 mBq l-1) is always higher than 210Po (mean: 4.1 ± 1.97 mBq l-1). The mean 210Po and 210Pb concentration in sand was 5.2 ± 1.87 and 3.1 ± 1.20 Bq kg-1, respectively; indicating that 210Po concentrations in the sand sample is always higher than that of 210Pb. The concentration of both 210Po and 210Pb depends on grain size of the sand. Surface samples of depth 0-10 cm recorded maximum 210Po (6.37 Bq kg-1) and 210Pb (4.07 Bq kg-1) concentration. The concentrations of 210Po and 210Pb in biota are following decreasing order: Oyster > Clam > Squid > Crab > Prawn > Fish. The committed effective dose rate calculated for shellfish species maintained a higher range of 81.0-281.2 µSv y-1. However, dose transfer rate from fish species fluctuated from 14.4 to 165.6 µSv y-1and this indicated that fish is radiologically safe as compared to shellfish.

A REVIEW ON VARIATION OF NATURAL RADIOACTIVITY ALONG THE SOUTHEAST COAST OF TAMIL NADU FOR THE PAST 4 DECADES (1974-2016).

This review deals with natural radioactivity variation along the southeast coast of Tamil Nadu for the past four decades (1974-2016). About 40 research works have been conducted along the coast since 1974 in various environmental matrices using a variety of experimental methods. For these measurements researchers are adopted different experimental methods. The measured gamma dose rate ranged from 30 to 8700 nGy/h. The mean specific activity of 238U, 232Th and 40K was found to be 58.8 ± 28.7, 465.2 ± 147.3 and 311.2 ± 27.8 Bq/kg, respectively. The calculated annual exposure rate ranged from 0.29 to 12.8 mSv/y with the mean value of 3.7 mSv/y which is above the global average of 2.4 mSv/y as reported by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) (Report to General Assembly, Annex B Exposures of the public and workers from various sources of radiation. United Nations, New York (2008)). Plant food items recorded low 210Po activities as compared to seafood organisms. Grain size, season and place of sampling have a decisive bearing on coastal radioactivity. Therefore, it is concluded from the review data that there is an appreciable elevation in background radiation level in the coastal region. This review suggests that new radiological surveys using improved methodology that cover the entire coastal stretch are needed.

Building Capability for Clinical Pharmacology Research in Sub-Saharan Africa.

A strong scientific rationale exists for conducting clinical pharmacology studies in target populations because local factors such as genetics, environment, comorbidities, and diet can affect variability in drug responses. However, clinical pharmacology studies are not widely conducted in sub-Saharan Africa, in part due to limitations in technical expertise and infrastructure. Since 2012, a novel public-private partnership model involving research institutions and a pharmaceutical company has been applied to developing increased capability for clinical pharmacology research in multiple African countries.

Population pharmacokinetics of ibandronate in Caucasian and Japanese healthy males and postmenopausal females.

INTRODUCTION: Ibandronate is a potent, nitrogen-containing bisphosphonate that is licensed as a once-monthly oral preparation and is currently in clinical development as a novel intermittent intravenous (i.v.) injection in osteoporosis. Ibandronate pharmacokinetic (PK) data were used to develop a PK model that could ultimately be incorporated into a PK pharmacodynamic (PD) model to assist the ibandronate development program through computer-assisted trial design. This manuscript reports the use of non-linear mixed-effects modeling to characterize the PK of ibandronate, to examine the possible influence of ethnicity on the disposition of ibandronate and to develop an appropriate population PK model for ibandronate. METHODS: A retrospective, cross-study population PK analysis was performed using PK data from five phase I studies with i.v. ibandronate (0.125 - 2.0 mg) conducted in Caucasian and Japanese healthy male volunteers, postmenopausal Caucasian women without osteopenia and postmenopausal Japanese women with osteopenia. The following covariates were investigated to establish their influence on the central volume of distribution (V1) and drug clearance (CL): age, body weight, gender, disease status (healthy versus osteopenic), creatinine clearance (CLCR), and ethnicity (Japanese versus Caucasian). Serum concentrations of ibandronate were quantified by GC-MS or ELISA, and data were modeled using non-linear mixed-effects modeling implemented by the software program NONMEM. RESULTS: The PK of ibandronate was adequately described by a linear 3-compartment model. Disease status, body weight, gender and CLCR significantly influenced ibandronate CL (10 34%) and the latter 3 also influenced V1 (20 29%). Ethnicity was not a determinant for ibandronate PK in the final model. Although gender was the most influential covariate, differences in V1 and CL between the sexes were modest (29 and 34%, respectively) and the overall effects on ibandronate exposure (Cmax and AUC) were not clinically relevant. The final model described the observed PK of ibandronate well, and all PK parameters were estimated with an acceptable degree of precision (SE < 13%). CONCLUSION: The PK of i.v. ibandronate was well described by a linear 3-compartment population PK model that included disease status, body weight, gender and CLCR as covariates, but without greatly affecting ibandronate exposure (Cmax and AUC). Ethnicity did not influence ibandronate PK and was not included in the final model.

Evaluation of wound healing activity of Vanda roxburghii R.Br(Orchidacea): a preclinical study in a rat model.

The extract of Vanda roxburghii was administered topically to rats at a dose of 150mgkg(-1) day(- 1) for 10 days and was studied for its effect on wound healing, using the excision wound model. A 60% reduction in wound diameter was observed in the test group rats receiving the extract compared to controls (48%). Significant increases in wet and dry granulation tissue weights (P < .001), hydroxyproline (P < .001), and hexosamine (P < .003) contents were detected. An increase in protein content was also detected in the test group (P > .05, ns). These findings are consistent with wound healing at cellular levels. The pro-healing action may be attributed either to increased collagen deposition or to better alignment and maturation or both. The test wounds (extract-treated wounds) were, on average, fully healed by the 13th day, whereas the control group healed, on average, by the 20th day. These data suggest that the extract of Vanda roxburghii administered topically has wound-healing potential in rats.

Human D2 and D4 dopamine receptors couple through betagamma G-protein subunits to inwardly rectifying K+ channels (GIRK1) in a Xenopus oocyte expression system: selective antagonism by L-741,626 and L-745,870 respectively.

To examine the effects of a novel selective D4 receptor ligand, L-745,870 (3-[4-(4-chlorophenyl)piperazin-1-yl]methyl-1H-pyrrolo[2,3-b]pyrid ine), on human dopamine receptor function, the ability of this ligand to antagonise G-protein gated inwardly rectifying K+ (GIRK/Kir3) currents activated by cloned human D2 and D4 receptors expressed in Xenopus oocytes was examined using voltage-clamp recording. Its effects were also contrasted with that of a selective D2 receptor antagonist L-741,626. L-745,870 had no detectable agonist activity on human D4 receptors and selectively blocked currents activated by D4 but not D2 receptors. The role of G-protein subunits in dopamine receptor modulation of GIRK currents was also examined by co-expression of beta1 and/or gamma2 subunits on spontaneously active and receptor-activated currents. Currents activated by both D2 and D4 receptors were occluded by direct activation of GIRK currents following co-transfection with the cDNA encoding G-protein betagamma subunits. These data demonstrate that L-745,870 and L-741,626 act as antagonists on human D4 and D2 receptors respectively, and that activation of GIRK channels by these dopamine receptors can be disrupted by direct stimulation of K+ currents by G-protein betagamma subunits.

Salicylidene salicylhydrazide, a selective inhibitor of beta 1-containing GABAA receptors.

1. A high-throughput assay utilizing the voltage/ion probe reader (VIPR) technology identified salicylidene salicylhydrazide (SCS) as being a potent selective inhibitor of alpha2beta1gamma1 GABA(A) receptors with a maximum inhibition of 56+/-5% and an IC(50) of 32 (23, 45) nm. 2. Evaluation of this compound using patch-clamp electrophysiological techniques demonstrated that the compound behaved in a manner selective for receptors containing the beta1 subunit (e.g. maximum inhibition of 68.1+/-2.7% and IC(50) value of 5.3 (4.4, 6.5) nm on alpha2beta1gamma1 receptors). The presence of a beta1 subunit was paramount for the inhibition with changes between alpha1 and alpha2, gamma1 and gamma2, and the presence of a subunit having little effect. 3. On all subtypes, SCS produced incomplete inhibition with the greatest level of inhibition at alpha1beta1gamma1 receptors (74.3+/-1.4%). SCS displayed no use or voltage dependence, suggesting that it does not bind within the channel region. Concentration - response curves to GABA in the presence of SCS revealed a reduction in the maximum response with no change in the EC(50) or Hill coefficient. In addition, SCS inhibited pentobarbitone-induced currents. 4. Threonine 255, located within transmembrane domain (TM) 1, and isoleucine 308, located extracellularly just prior to TM3, were required for inhibition by SCS. 5. SCS did not compete with the known allosteric modulators, picrotoxin, pregnenolone sulphate, dehydroepiandrosterone 3-sulphate, bicuculline, loreclezole or mefenamic acid. Neither was the inhibition by SCS influenced by the benzodiazepine site antagonist flumazenil. 6. In conclusion, SCS is unique in selectively inhibiting GABA(A) receptors containing the beta1 subunit via an allosteric mechanism. The importance of threonine 255 and isoleucine 308 within the beta1 subunit and the lack of interaction with a range of GABA(A) receptor modulators suggests that SCS is interacting at a previously unidentified site.

Induction of apoptosis in human lung cancer cells by curcumin.

Curcumin, a phenolic compound from the rhizome of the plant Curcuma longa has anti-inflammatory, antioxidant and anti-cancer activities. Although the precise mode of action of this compound is not yet elucidated, studies have shown that chemo-preventive action of curcumin might be due to its ability to induce apoptosis and to arrest cell cycle. This study investigated the cellular and molecular changes induced by curcumin leading to the induction of apoptosis in human lung cancer cell lines-A549 and H1299. A549 is p53 proficient and H1299 is p53 null mutant. The lung cancer cells were treated with curcumin (0-160 microM) for 12-72 h. Curcumin inhibited the growth of both the cell lines in a concentration dependent manner. Growth inhibition of H1299 cell lines was both time and concentration dependent. Curcumin induced apoptosis in both the lung cancer cell lines. A decrease in expression of p53, bcl-2, and bcl-X(L) was observed after 12 h exposure of 40 microM curcumin. Bak and Caspase genes remained unchanged up to 60 microM curcumin but showed decrease in expression levels at 80-160 microM. The data also suggest a p53 independent induction of apoptosis in lung cancer cells.

Studies of water movement across the gut using oral rehydration solutions in a rat perfusion model.

AIM: To measure water influx and efflux, as well as net water, sodium and potassium absorption from a range of oral rehydration solutions (ORS) in which the glucose content had been partially replaced with the amino acid leucine or with food supplements. METHODS: A series of in vivo steady-state perfusion studies in normal rat intestine. The oral rehydration solutions contained 60 or 90 mmol/L of sodium. The reference solution used was the World Health Organization (WHO) formula. RESULTS: There was a significant negative correlation between the oral rehydration solution osmolality and net water absorption (r = -0.722, P < 0.05). The highest net water absorption occurred using comminuted chicken supplemented oral rehydration solution containing 60 mmol/L sodium (P < 0.001). This oral rehydration solution also showed a significant increase in the rate of influx of water (P < 0.05) in comparison with the WHO formula containing 60 mmol/L sodium. CONCLUSION: This work provides further evidence that food-based oral rehydration solutions, including non-vegetable sources, may have a useful role to play in the management of patients with acute diarrhoea.

Clinical implications of cytogenetic classification in adult acute lymphoblastic leukaemia patients.

Cytogenetic analysis performed on pretreated unstimulated, bone marrow/peripheral blood samples of 46 adult patients with acute lymphoblastic leukaemia (ALL) showed sufficient metaphases in 39 patients and insufficient metaphases in 7 patients. G-banded karyotype analysis of these 39 patients revealed non-random clonal chromosome abnormalities in 31 patients and apparently normal karyotypes in 8 patients. Numerical abnormalities involving chromosome trisomies and structural abnormalities involving different types of chromosomal translocations and deletions were encountered in varying percentages. These patients were grouped into various cytogenetic subsets on the basis of their karyotype pattern and followed-up to evaluate their prognosis. Patients with apparently normal karyotypes showed good prognosis and those with 6q- showed intermediate prognosis. But all other patients with hyperdiploid, pseudodiploid and hypodiploid karyotypes were associated with poor prognosis. Cytogenetic classification of ALL patients is thus of clinical importance, as it helps the early identification of clinically important prognostic groups.

Pharmacology of recombinant human GABA(A) receptor subtypes measured using a novel pH-based high-throughput functional efficacy assay.

To facilitate the discovery of novel compounds that modulate human GABA(A) receptor function, we have developed a high throughput functional assay using a fluorescence imaging system. L(tk-) cells expressing combinations of human GABA(A) receptor subunits were incubated with the pH-sensitive dye 2',7'bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein, then washed and placed in a 96-well real-time fluorescence plate reader. In buffer adjusted to pH 6.9 there was a robust and persisting acidification response to addition of GABA, which was antagonised by the GABA(A) receptor antagonist bicuculline. The concentration-response relationship for GABA was modulated by allosteric ligands, including benzodiazepine (BZ) site agonists and inverse agonists. The effects of BZ site ligands on the pH response to GABA for receptors containing alpha1beta3gamma2, alpha3beta3gamma2 or alpha5beta3gamma2 subunits were well correlated with results from electrophysiological studies on the same receptor subunit combinations expressed in Xenopus oocytes. Most modulatory compounds tested were found to be relatively unselective across the three subunit combinations tested; however, some showed subtype-dependent efficacy, such as diazepam, which had highest agonist effects on the alpha3beta3gamma2 subtype, substantial but lesser agonism on alpha1beta3gamma2 and still substantial but the least agonism on alpha5beta3gamma2. This indicates that the alpha subunit within the recombinant receptor expressed in L(tk-) cells can affect the efficacy of the response to some BZ compounds. Inhibitors of Na(+)/Cl(-) cotransport, anion/anion exchange and the gastric type of H(+)/K(+) ATPase potently inhibited GABA-evoked acidification, indicating that multiple transporters are involved in the GABA-evoked pH change. This novel fluorescence-based high throughput functional assay allows the rapid characterization of allosteric ligands acting on human GABA(A) receptors.

Nonrandom karyotype abnormalities in 36 multiple myeloma patients.

G-banded analysis performed on pretreated bone marrow samples of 36 multiple myeloma patients allowed the identification of clonal chromosome abnormalities. Abnormalities consisting of trisomies, monosomies, translocations, deletions, and marker chromosomes apparently followed a nonrandom pattern. The chromosomes involved in the production of abnormal karyotypes were numbers 1,2,3,11,12,14,17, and 18. Even though no specific chromosome pattern has been identified, the involvement of chromosomes 1, 3, and 14 was found to be more frequent. Many of the chromosomes and chromosomal breakpoints involved in these abnormalities correspond to the location of identified oncogenes or tumor suppressor genes. Hence, it is presumed that these chromosome abnormalities may be playing an important role in the genesis of multiple myeloma by altering the structure or function of oncogenes or tumor suppressor genes.

A retrospective study of human immunodeficiency virus infection and drug-resistant tuberculosis in Durban, South Africa.

SETTING: King George V hospital, a specialist referral hospital for tuberculosis (TB) patients in Durban, South Africa. OBJECTIVE: To investigate the relationship between drug-resistant TB and human immunodeficiency virus (HIV) infection. DESIGN: Retrospective descriptive study of 295 patient records, for the period January 1991 to April 1994, which were reviewed to collect data on HIV status, drug susceptibility and outcome as well as age, race, gender and previous TB treatment. RESULTS: Overall, 42 patients (14.2%) were HIV-seropositive while the rate of multidrug-resistant TB (MDR-TB) was 10.2%. Of those previously treated, 6.1% were HIV-seropositive while of those with no known history of previous TB, 5.4% were HIV-seropositive. A history of previous antituberculosis treatment was the strongest predictor for the presence of organisms resistant (Odds Ratio = 3.1; P = 0.0016) to one or more of the antituberculosis drugs. The prevalence of HIV infection was 13.1% in patients with drug-resistant TB and 14.9% in patients with drug-sensitive TB. CONCLUSION: The HIV epidemic has not exacerbated the occurrence of drug-resistant TB. History of previous TB treatment, and not HIV infection, was the principal factor associated with TB which is resistant to at least one primary anti-TB drug. However, as the HIV epidemic progresses in a milieu of high TB prevalence, the link with drug-resistant TB warrants constant monitoring and investigation.

The potential use of urinary excretion data for assessing the relative bioavailability of rifampicin in fixed dose combination anti-tuberculosis formulations.

SETTING: The perceived need for simple, non-invasive methods of assessing the relative bioavailability of rifampicin in fixed-dose combination (FDC) anti-tuberculosis formulations. OBJECTIVE: To compare the performance of methods based on urinary excretion data with those utilising plasma concentration-time profiles to assess the relative bioavailability of rifampicin in combined and single-drug formulations. DESIGN: A two-period randomised crossover bioequivalence study in healthy male volunteers with a 1 week washout period between treatments. Plasma rifampicin concentrations were measured at 0, 1, 2, 4, 6 and 8 hours after each drug administration using a high performance liquid chromatography (HPLC) method. The rifampicin and desacetylrifampicin content of complete urinary collections made from 0-4 and 4-8 hours after dosage were determined using both the HPLC and a much simpler colorimetric procedure. RESULTS: There was good agreement between the relative bioavailability of the formulations using plasma and urinary excretion data, although the precision of the urinary-based estimates was slightly less than those derived from the plasma findings. There was also good agreement between the HPLC and colorimetric estimates of the combined urinary excretion of rifampicin plus desacetylrifampicin. CONCLUSIONS: Urinary excretion data may be used for ongoing quality control to confirm that commercial combined rifampicin-containing formulations that were initially shown to be satisfactory continue to be so.