1 It is found in wooded areas of Senegal, southern part of Nigeria, Central and Eastern Africa. 2 It is used for the treatment of backache, diabetes and as an anti-scorbutic. The leaves of the plant boiled in its own sap are used for the treatment of gastrointestinal sores. 1 Its sap is used for toothache and cough. 3 It is used in the treatment of jaundice and haemorrhoids among the Baka Pygmies of Cameroon and also used in the traditional

treatment of inflammatory, skin infection and ulcer. 4 and 5 The presence of alkaloids, tannins, saponins, phlobatannins, terpenoids and flavonoids in the leaves of T. potatoria has been reported. 6T. potatoria root has also been found to contain phytochemicals such as tannins, flavonoids, phlobatannins and cardiac glycosides. 7 Betulinic acid, 3β-hydroxy-lup-20(29)-en-28-oic acid, a C-28 carboxylic acid derivative of the ubiquitous triterpene INK1197 chemical structure betulin, is a member of the class of the lupane-type pentacyclic triterpenes. Figure options Download full-size image Download as PowerPoint slide It was isolated at the beginning of the 20th century and originally called gratiolone.8 However unlike betulin, the oxidized derivative

Everolimus datasheet betulinic acid possesses a number of intriguing pharmacological effects including: anti-inflammatory, anticancer and anti-HIV.5, 9 and 10 T. potatoria root was collected from Ilesa, Osun state, Nigeria and authenticated by Mr. G. Ibhanesebhor, plant taxonomist, Herbarium, Obafemi Awolowo University, Ile-Ife, Nigeria. Voucher specimen (IFE Herbarium 16419) was deposited in the herbarium. The plant material Carnitine dehydrogenase was air-dried, pulverised

and extracted by soaking 1.2 kg sample in aspirator bottles containing distilled methanol at room temperature (25 °C) for 48 h. The extract was filtered and solvent was completely removed by vacuum evaporator at 50 °C to give viscous mass (18.55 g, 1.5% yield), which was stored inside a dessicator for further usage. Phytochemical screenings of MeTp were performed using standard procedures.11, 12 and 13 0.5 g of the extract was boiled with 10 ml of sulphuric acid (H2SO4) and filtered hot. The filtrate was shaken with 5 ml of chloroform. The chloroform layer was pipetted into another test tube and 1 ml of dilute ammonia solution was added. The presence of pink colour in the aqueous layer indicated the presence of anthraquinones. 5 ml dilute ammonia was added to a portion of an aqueous filtrate of the extract. Concentrated sulphuric acid (1 ml) was added. A yellow colouration that disappears on standing indicates the presence of flavonoids. About 0.5 g of the extract was boiled in 10 ml of water in a test tube and then filtered. A few drops of 0.1% ferric chloride was added and observed for brownish green or a blue-black colouration. To 0.5 g of extract was added 5 ml of distilled water in a test tube. The solution was shaken vigorously and observed for a stable persistent froth.

Then the vessel was removed from the fire. While hot condition, the mixed powders of ingredients 1–16 were added and mixed thoroughly to prepare the homogenous product. The product was allowed

to cool at room temperature and packed in tightly closed containers to protect from light and moisture. The drug sample (5 g) was weighed MI-773 mw and mixed with 50 ml of water in a beaker with gentle warming, till the sample completely dispersed in water. The mixture was centrifuged and decanted the supernatant. The sediment was washed several times with distilled water, centrifuged again and decanted the supernatant. A few mg of the sediment was taken and mounted in glycerin. Then few mg was taken in watch glass and added few drops of phloroglucinol and concentrated hydrochloric acid, mounted in glycerin. The salient Panobinostat in vitro microscopic features of the drug were observed in different mounts.4 All the three batch samples were subjected for the analysis of physico-chemical studies like total ash, acid insoluble ash, water soluble ash, solubility in alcohol and water and for

loss on drying at 105 °C. Bulk density, sugar estimation and pH values for 1% and 10% aqueous solution were also carried out.5 All the three samples (2 g) were soaked in chloroform and alcohol separately for 18 h, refluxed for 10 min on water bath and filtered. The filtrates were concentrated on water bath and made up to 5 ml in a standard flask separately.

Both chloroform and alcohol extracts were applied on pre-coated silica gel 60 F254 TLC plate (E. merck) as absorbent and developed the plate using solvent systems, toluene:ethyl acetate 9:1 and 6:4 respectively. After developing, the plates were dried and observed the colour spots at UV 254 nm, UV 366 nm and vanillin–sulphuric acid spraying reagent.6 The other parameters such as found microbial load and heavy metal were carried out as per the WHO guidelines.7 Aflatoxin and pesticide residues were carried out by standard methods.8 Jawarish-e-Jalinoos is brown in colour, semi-solid, characteristic of its own odour and sweetish bitter in taste. The samples were spreaded in a petridish and observed. No filth, fungus or objectionable extraneous matters were found in the samples. The salient features of raw drugs in Jawarish-e-Jalinoos were observed and the microscopical photographs are shown in Fig.

This measure asks adolescents how many vehicles and computers their family owns, whether they have a bedroom to themselves

and how many holidays they have had with their family in the past year. Items were summed to give an overall family affluence score (range 0–10), which was split into tertiles: ‘low’ (scores of 0–4), ‘medium’ (scores of 5–6) and ‘high’ (scores of 7–10). Participants were asked whether they smoked (yes/no). Sexual experience was assessed by asking participants ‘Have you ever had vaginal sex?’ (yes/no); this question was adapted from the ‘National Survey TSA HDAC concentration of Sexual Attitudes and Lifestyles’ [17]. Expectation of having sex in the next year was also assessed using two items adapted from Sheeran and Orbell [36]: ‘I expect I will have sex this year’ and ‘I think I will have sex this year’ (5-point scale: ‘strongly disagree’ to ‘strongly agree’, scored from 1 to 5). These items correlated highly (r = 0.97) and were summed to give an overall score which was split into tertiles: ‘no expectation’ (scores of 2), ‘low expectation’ http://www.selleckchem.com/products/Fasudil-HCl(HA-1077).html (3–5) and ‘high expectation’ (6–10)

of having sex in the next year. Intention to attend cervical screening in the future was assessed using similar items: ‘When I am older and am invited to go for a smear (Pap) test, I intend to go’ and ‘When I am older and am invited to go for a smear (Pap) test, I will try to go’ (with a 5-point response scale as before). The items correlated highly (r = 0.89) and were summed to give an overall screening intention score which was split into Mannose-binding protein-associated serine protease tertiles: ‘low intention’ (scores of 2–6), ‘medium intention’ (7–8) and ‘high intention’ (9–10). Other measures in the questionnaire that are not reported here have been described elsewhere [34]. After reading a brief description of the HPV vaccine (see Box 1) participants were asked to indicate their vaccine status (response options: ‘I have had all 3 doses of the HPV vaccine’; ‘I have had 1 or 2 doses of the HPV vaccine’; ‘I have been offered the HPV vaccine but I haven’t had it’; ‘I have not been offered the HPV vaccine’;

‘I don’t know’). Human papillomavirus (HPV) is a very common infection involved in most cervical cancer. It is transmitted via skin-to-skin contact, most commonly during sexual activity. A vaccine was developed that protects against this infection. You should have been offered the HPV (cervical cancer) vaccine in Year 8. It involved having three injections over about 6 months. Logistic regression analyses, clustering by school and cohort, were used to examine the association between HPV vaccine status (fully vaccinated versus un-/under-vaccinated) and other risk factors for cervical cancer. It is necessary to adjust for clustering of data within schools and cohorts in order to obtain unbiased tests of significance. Analyses were performed using the Complex Samples function in SPSS v.20 [37].

The effluent was analysed by APHA, 1981.3 The fresh material of plant was collected from both sites non-polluted (ALTT Centre) and polluted (cycles manufacturing unit) area of Ghaziabad, UP, India. For colour reaction test Cromwell, 19554 & Trease and Evans, 19835 were followed. TLC was done According to the WHO, Geneva, 1998.6 Chlorophyll a, b and total chlorophyll (a + b) were determined according to Arnon, 1949.7 The effluent was analysed and the results are given in Table 1. The result shows the presence of alkaloids, saponin, tannin, lignin, protein, carbohydrate, suberin, glucoside, oil, sugars, steroids and absence of flavanoids in both the cases. Degree of change in colour reaction tests are

tabulated in Table 2. From the observation of TLC, it is found that the number of spots were higher in non-polluted plants than the polluted plants (Plate 1). The RF values are tabulated in Table 3. Chlorophyll a, chlorophyll b and see more total chlorophyll were observed 76.98%, 86.29% and 80.10% of control leaves samples (Plate 2). The results are tabulated in Table 4. The effluent samples collected from the industry selected for this study was

analysed for different physico-chemical parameters which showed higher values as compared to the standard values recommended by the Indian Standard Institute (I.S.I.; 1974, 1974 and 1977). Similar results were also obtained by Kumar, et al,1988.8 A critical observation on the data studied clearly indicate that plants growing at polluted sites were badly affected and there were a significant reduction GSK2656157 order in number of parameters studied as compared to the plants growing at the control sites. Major qualitative changes, noticed under the impact of industrial effluent, are reduction in chlorophyll level, photosynthesis rate, accumulation of heavy metals, alternation in pH, BOD, COD, Colour, Temp, Odour, TS, TDS. Heavy metals resulted into reduced growth and yield in comparison to plant species growing at non-polluted sites. The impact of industrial effluent on the qualitative and quantitative

values of medicinal plants does not appear to have been undertaken much till now. Colour reaction tests showed the degree of changes in plants of polluted sites. From the observations some alteration in the bio-chemical parameters were also recorded in plants growing Resveratrol near the industrial effluent. The amount of chemical constituents found to have decreased in those plants which were growing in polluted areas. From the observations of TLC, it was seen that the number of spots were decreased in the plant samples of polluted sites. From the findings of this investigation it may be ascertained that there had been qualitative and quantitative alternations in the chemical constituents in the plants growing in industrial areas. It can also be stated that industrial pollution may also have lowered the drug potency of the plants growing in the vicinity of industries.

A total of 520 case studies were completed. Although responding to all questions was not mandatory, there were less than 3% incomplete responses to quantitative questions (including the Anti-Fat Attitudes questionnaire) and 31% for free-text responses, which was sufficient for all power selleck calculations. Anti-Fat Attitudes questionnaire

results, presented in Figure 2, indicated negative attitudes by the participants towards people who are overweight, with a mean item score of 3.2 (SD 1.1), where results greater than zero indicate weight stigma.29 These results are considerably higher than other Australian and international Anti-Fat Attitudes questionnaire findings from 2001,38 and similar to Australians tested in 2007.32 The Willpower subscale had a mean item ABT-199 datasheet score of 4.9 (SD 1.5) and the Fear subscale a mean item score of 3.9 (SD 1.8), which were relatively higher mean scores than the Dislike subscale of 2.1 (SD 1.2). This finding of overtly negative attitudes towards people who are overweight or obese indicates that physiotherapists demonstrate explicit weight stigma. There was minimal indication in the clinical parameters tested in the case studies, such as the total treatment time or the hands-on treatment time, that patients in different BMI categories would be treated differently.

These data are presented in Table 2, Table 3 and Table 4. The only differences that reached significance were three (6%) of the answers to questions about types of treatment likely to be given. This indicates a minimal difference in (hypothetical) treatment of patients

due to the BMI. Of note, however, for case study 2, general health advice was prescribed in 46% of the obese patients, which was significantly greater than 24% in the normal weight case study presentation (p < 0.01). This could indicate implicit weight stigma, in that physiotherapists may assume patients who are obese are less well informed about general health than their normal weight counterparts. There was no indication of implicit weight stigma in findings from participants’ responses to questions (for wording see Appendix 1) about their level of professional satisfaction (p = 0.45) or enjoyment (p = 0.98) when treating patients in the case studies, with no difference found between normal and overweight patients. However, when participants Sclareol were asked to rate how similar they felt to case study patients, participants felt more similar (p = 0.05) to patients who are overweight (mode ‘not similar’) in comparison to normal weight (mode ‘not similar’). Feeling similar to someone has been correlated with liking them, 39 so this finding on its own would not indicate negative attitudes, although this may fit with the ‘jolly fat’ stereotype, 40 so may indicate weight stigma. Analysis of the two questions requiring free-text responses identified that conversations about weight are likely to occur.

Significantly more of the males lived in urban areas of The Gambia compared to females, and

the distribution of month of study differed between the males and females recruited. No differences were observed in age, waist:hip ratio, or serum neopterin levels between the male and female subjects. Pre- and post-vaccination geometric mean (95% CI) data for both the pneumococcal and Vi vaccine are detailed in Table 3. A total of 112 subjects (37.2%) did not achieve antibody titres >3.52 EU following Vi vaccination, the estimated level for 90% protection. Using a post-vaccination anti-pneumococcal IgG titre of >0.35 μg/mL, the level considered indicative of putative protection, all subjects achieved an adequate response to all serotypes. Simple univariate selleck chemicals regression analysis was used to test for unadjusted associations between antibody response to vaccination and the contemporary variables measured at the time of vaccination; sex, age, location (rural vs. urban), weight, height, BMI, plasma leptin, month of study (February, March, April, May), malaria parasitaemia (+ve vs. −ve), and serum neopterin levels ( Table 4). Pre-vaccination antibody titres were also included as a potential confounder in all of the models. Variables showing significant associations with antibody response to vaccination were then fitted into a multivariate model; those variables that remained significant

are as detailed in Table 4. Only those variables that remained significant predictors of antibody response were then added to the models looking at early-life influences on response Ketanserin to vaccination. Pictilisib We did not predict, a priori, that pre-vaccination antibody levels would have such a strong influence on post-vaccination antibody responses. However, and as pre-vaccination levels could themselves be predicted by early life exposures (through immune responses to infection), we repeated the analysis (a) looking at predictors of pre-vaccination levels per se, and (b) removing pre-vaccination levels from the final model of predictors of post-vaccination levels. Following

adjustment for contemporary factors shown to be associated with pre-vaccination levels, the only significant association observed was between infant weight at 12 months of age and pre-vaccination levels to pneumococcal serotypes 5 and 23 (p = 0.028 and 0.016 respectively; analyses not presented). The results of the regression analysis excluding pre-vaccination levels are included in Table 5. Associations between early-life exposures and antibody responses to vaccination were tested by multiple linear regression analysis, adjusting for the contemporary variables identified as predictive of antibody responses. Table 5 highlights the unadjusted and adjusted results of multiple linear regression analysis using birth weight, low birth weight (<2.5 kg) vs.

, 2011) should boost research output regarding the (epi)genomic action of GR and MR during the coming years. It’s becoming increasingly PLX4032 in vivo clear that glucocorticoids act on neuronal function through a great number of molecular mechanisms within different time domains. The fastest action is via membrane-bound

receptors (Groeneweg et al., 2012), an issue which hasn’t been addressed as their role in the behaviors mentioned here is unclear. The second fastest is the interaction of receptors with signaling mechanisms like the GR-MAPK interaction addressed here. The slowest one is the action of MRs and GRs (via GREs) at the genome. This molecular portfolio allows glucocorticoids to adjust neuron function via disparate mechanisms and different time domains, which underscores its importance for resilience. It is now well established that life style choices play a pivotal role in staying healthy and well, selleck screening library both physically and mentally. A life style option which has been obtaining great attention over the past several decades is physical activity. Initially, great benefits as a result of performing exercise regularly were seen with regard to cardiovascular health and controlling body weight. Presently, however, it has become clear that regular physical activity evokes vast changes in a plethora of body functions, many of which can be regarded as particularly

beneficial for resilience. As the breadth of its effects on the body and mind is probably greater than any other life style option (e.g. meditation, yoga) we have chosen to review

here the consequences of regular exercise with special emphasis regarding its benefits for stress resilience. During the past 15 years evidence has been accumulating before that an active life style is beneficial for resilience against stress. Often (in the media) it is thought that regular exercise is predominantly helpful for cardiovascular health and maintaining body weight in a healthy range. However, a variety of studies, exploring effects of exercise at the molecular, cellular, physiological and behavioral level, have shown that exercise has a deep impact on many body functions. When considering animal studies a distinction needs to be made between voluntary exercise and forced exercise. In the voluntary exercise paradigm, rodents like rats and mice run in a running wheel whenever they please to do so; they are not forced whatsoever. If provided with a running wheel they will run during the first half of the nighttime, i.e. the time when they are normally most active (Droste et al., 2003 and Droste et al., 2007). A vast body of work indicates that this voluntary exercise has major beneficial effects and increases resilience to stress (Reul and Droste, 2005, Collins et al., 2012 and van Praag et al., 1999).

All samples described above were quantified using fresh calibration curve and compared to freshly prepared quality control samples at the same concentration level. Liquid chromatography coupled with the mass spectrometer (LC–MS/MS) has now become a universally acceptable technique for the estimation of drugs from the biological fluids as part of bioequivalence evaluations. Donepezil and internal

standard were scanned in the positive mode for the parent ion and reproducible daughter ion and the m/z ratio of 380.2/91.2 and 387.3/98.2 respectively were selected for donepezil and internal standard. The quantification was performed in Multiple Reaction Monitoring (MRM) selleck products mode in analyst software. The compound specific mass spectrometric parameters are optimized to produce the reproducible responses for the analyte and internal

standard. Chromatographic conditions are optimized to achieve good resolution and symmetric peak shape for the analyte at the lower level of quantification. The chromatographic conditions like flow rate (1.0 ml/min) Everolimus datasheet and column (C18 column) conditions were also optimized with the runtime of 4 min. The analyte and internal standard were quantified at 1.8 min. Other conditions are optimized for the reproducible quantification method. Liquid–liquid extraction technique was chosen for the simple and cost effective extraction procedure and the conditions are optimized to yield cleaner extract of the sample to avoid the quantification issues with the LCMSMS. Protein precipitation with acetonitrile was tried but the recovery was found to be low. Organic solvent mixture consisting of dichloromethane and hexane was yielded good recovery and better chromatography compared to individual solvents. Sample volume of 300 μl was optimized to have the sensitivity and quantifiable

and acceptable peak shape at the lower limit of quantification of 50 pg/ml. Lesser sample volumes are also attempted but the peak shape and response at the lower limit of quantification are not acceptable Thiamine-diphosphate kinase with respect to signal to noise ratio. The quality control samples were prepared at the concentrations specified in the bioanalytical method validation guidelines. The LOQQC was prepared at approximately same concentration of lowest calibration standard. The LQC was prepared at the concentration less than three times of lowest calibration standard. MQC concentration was prepared at approximately 35% of the highest calibration standard. HQC concentration was prepared at the concentration of approximately 70% of the highest calibration standard. The LCMSMS method was selective for the intended analyte since the quantification is based on the mass to charge ratio of parent as well as product ion in MRM transition mode which are selective and specific.

Creamy solid (92%), mp 127–132 °C; C26H21ClN2O3; IR (KBr) 2302.0 (s), 1650.95 (m), 1604.66 (s), 1542.95 (s), 1488.94 (w), 1458.08 (m), 1434.94 (m), 1342.36 (w), 1265.22 (w) cm−1; 1H NMR δH (CDCl3, 300 MHz): 8.09 (d, 1H, J = 8.4, C10-H), 7.50–7.44 (m, 7H, Ar-Hs), 7.40–7.25 (m, 5H, Ar-Hs), 7.05 (d, 1H, J = 2.1 Hz, Ar-H), 4.77 (d, 1H, J = 2.7 Hz, C3H), 4.36 (d, 1H, J = 5.4 Hz, C11b-H), 4.25 (d, 1H, J = 11.4 Hz, C4H), 3.85–3.79 (m, 1H, C4H), 3.08 (s, 3H, NCH3), 2.68–2.62 (m, 1H, C3aH); 13C NMR δC (CDCl3, 75 MHz): 174.37 (C O), 158.60 click here (C5a), 153.0 (C6a), 141.43 (q), 140.39 (q), 132.78 (CH), 129.56 (CH), 128.33 (CH), 127.54 (CH), 127.25 (CH), 126.50 (CH), 126.36 (CH), 125.64 (CH), 124.74 (CH), 121.50 (C10a), 116.29 (C7), 96.21 (C11a), 82.45 (C3), 60.67 (C11b), 51.69 (C4), 46.39 (NCH3), 44.80 (C3a); m/z (ESI) 467.1 (M+ + Na). Creamy solid (85%), mp 138–142 °C; C21H20N2O3;

IR (KBr): 2310.2 (s), 1650.95 (m), 1612.38 (m), 1542.95 (w), 1488.94 (w), 1473.51 (w), 1296.08 (w) cm−1; 1H NMR δH (CDCl3, 300 MHz): 8.9 (d, 1H, J = 1.5 Hz, C10H), 7.46–7.41 (m, 4H, Ar-Hs), 7.34–7.10 (m, 3H,

Ar-Hs), 6.89 (d, 1H, J = 8.4 Hz, Ar-H), 4.30 (t, 1H, J = 7.5 Hz, C3H), 4.11 (d, 1H, AZD6244 J = 5.1 Hz, C4H), 4.03 (d, 1H, J = 11.7 Hz, C11b-H), 3.86–3.60 (m, 2H, C3-H & C4-H), 2.95 (s, 3H, N-CH3), 2.81–2.78 (m, 1H, C3a-H); 13C NMR δC (CDCl3, 75 MHz): 175.50 (C O), 159.11 (C5a), 151.60 (C6a), 142.36 (q), 134.36 (CH), 133.36 (CH), 129.73 (CH), 127.48 (CH), 126.36 below (CH), 126.03 (CH), 123.06 (C10a), 116.51 (C7), 93.64 (C11a), 69.02 (C3), 61.58 (11b), 52.10 (C4), 43.36 (N CH3), 38.72 (C3a); m/z (ESI) 371 (M+ + Na). Creamy solid (92%), mp 117–120 °C; C27H24N2O3; IR (KBr) 2360.71 (s), 1650.95 (m), 1612.38 (m), 1542.95 (s), 1488.94 (s), 1473.51 (w), 1357.79 (w), 1288.36 (m), 1218.93 (w) cm−1; 1H NMR δH (CDCl3, 300 MHz): 7.93 (d, 1H, J = 1.5, C10-H), 7.46–7.41c (m, 7H, Ar-Hs), 7.37–7.19 (m, 5H, Ar-Hs), 6.9 (d, 1H, J = 8.4 Hz, Ar-H), 4.36 (d, 1H, J = 4.8 Hz, C3H), 4.10 (d, 1H, J = 7.0 Hz, C11b-H), 4.23 (d, 1H, J = 11.4 Hz, C4H), 3.82–3.76 (m, 1H, C4H), 3.05 (s, 3H, NCH3), 2.62–2.41 (m, 1H, C3aH); 13C NMR δC (CDCl3, 75 M Hz): 174.91 (C O), 158.87 (C5a), 152.65 (C6a), 141.41 (q), 140.36 (q), 131.91 (CH), 129.17 (CH), 128.35 (CH), 127.90 (CH), 127.00 (CH), 126.26 (CH), 126.42 (CH), 125.64 (CH), 124.56 (CH), 122.66 (C10a), 116.18 (C7), 95.95 (C11a), 82.13 (C3), 60.50 (C11b), 51.32 (C4), 46.19 (NCH3), 44.59 (C3a); m/z (ESI) 447.1 (M+ + Na).

The oral bioavailability of DNDI-VL-2098 was good to excellent in all four

species ( Table 2). DNDI-VL-2098 showed close to dose proportional exposures in rodents (Table 2). Oral exposure in hamster and mouse were determined across the 6.25–50 mg/kg range (doses tested for efficacy) using formulations identical to those used in efficacy studies. In both species, bioavailability was 100% at the lowest 6.25 mg/kg dose, and in both species an 8-fold increase in dose (from 6.25 to 50 mg/kg) led to an 11-fold increase in exposure. In NSC 683864 manufacturer rat, oral exposures were determined across the 5–500 mg/kg dose range (doses tested in early safety studies) using a suspension in CMC. Here, a 100-fold increase in dose led to about a 100-fold increase in exposure. Fig. 3a summarizes the relationship between dose and dose-normalized AUCs (DNAUC) in various species following suspension administration. The dose-normalized AUCs of DNDI-VL-2098 were generally independent

(within 2-fold) see more of the administered doses. In the rat and dog, oral solution and suspension exposures were determined at 5 mg/kg. In both species, the mean solution exposure was higher than that with suspension (Fig. 3b). In the dog at the higher dose of 50 mg/kg given as suspension, exposure did not increase proportionally (Table 2). A similar “apparent solubility limited absorption” did not occur in the rat where exposures increased dose-proportionally up to 500 mg/kg given as suspension. This observation is consistent with DNDI-VL-2098 being a low solubility/high permeability compound, with the high permeability overriding any limitation that low solubility may pose to absorption, at least in the rat. Because exposures increased proportionally with dose in the rat at high doses, follow up studies were performed in the dog at higher doses using a corn oil formulation.

As solubility of DNDI-VL-2098 was less in water, an oil-based formulation using corn oil was evaluated. In this case, a 100-fold increase in dose from 5 mg/kg to 500 mg/kg, led to a 37-fold increase in exposure (AUClast). By using a 500 mg/kg BID dosing (dosed 8 h apart; total dose 1000 mg/kg), there was found a 50% increase in exposure (360 ± 36 μg h/mL; n = 3) compared to that obtained at the 1250 mg/kg QD dose (246 ± 74 μg h/mL; n = 3, Fig. 4). The preclinical PK parameters were used to perform allometric scaling to predict pharmacokinetics in humans. First, simple allometric scaling of the clearance and volume of distribution data was performed using Y = aWb, where Y is the parameter of interest, and a and b are coefficient and exponent of the allometric equation, respectively, and W is body weight. The clearance exponent calculated with this approach was 0.9. Because it exceeded 0.7, the maximum lifespan potential (MLP (years) = (185.4) (Br0.636) (BW−0.225)) approach was used ( Mahmood, 2007). The MLP method gave estimates of 1.