Muscle and feather in tissue of 40 juveniles and 40 adult green-lipped mussel Perna veridis (L.) collected from Muar Estuary, Johor were analyzed for copper (Cu), cadmium (Cd), lead (Pb) and zinc (Zn) concentration using a fast and sensitive Inductively Coupled Plasma Mass Spectrometer (ICP-MS). In this study, the average concentration of Cu was 8.96 microg g(-1) dry weights, Cd with 0.58 microg g(-1) dry weight, Pb averaging 2.28 microg g(-1) dry weights and Zn averaged to 86.73 microg g(-1) dry weight. The highest accumulation of metal studied was found in feather sample compared to the muscle. The positive relationship of Cu, Cd, Pb and Zn with P. virdis length suggesting that the accumulation of these metals were formed in the mussel. In all cases, metal levels found were lower than the guideline of international standards of reference and the examined bivalve were not associated with enhanced metal content in their tissues and were safe within the limits for human consumption.
Matched MeSH terms: Water Pollutants, Chemical/pharmacokinetics; Metals, Heavy/pharmacokinetics
Multivariate analysis including correlation, multiple stepwise linear regression, and cluster analyses were applied to investigate the heavy metal concentrations (Cd, Cu, Fe, Ni, Pb, and Zn) in the different parts of bivalves and gastropods. It was also aimed to distinguish statistically the differences between the marine bivalves and the gastropods with regards to the accumulation of heavy metals in the different tissues. The different parts of four species of bivalves and four species of gastropods were obtained and analyzed for heavy metals. The multivariate analyses were then applied on the data. From the multivariate analyses conducted, there were correlations found between the soft tissues of bivalves and gastropods, but none was found between the shells and the soft tissues of most of the molluscs (except for Cerithidea obtusa and Puglina cochlidium). The significant correlations (P < 0.05) found between the soft tissues were further complemented by the multiple stepwise linear regressions where heavy metals in the total soft tissues were influenced by the accumulation in the different types of soft tissues. The present study found that the distributions of heavy metals in the different parts of molluscs were related to their feeding habits and living habitats. The statistical approaches proposed in this study are recommended for use in biomonitoring studies, since multivariate analyses can reduce the cost and time involved in identifying an effective tissue to monitor the heavy metal(s) bioavailability and contamination in tropical coastal waters.
Matched MeSH terms: Water Pollutants/pharmacokinetics; Metals, Heavy/pharmacokinetics
This study was conducted to examine the effect of malathion on the development of Chrysomya megacephala. A total of 12 adult Sprague-Dawley rats was divided into 4 groups. Each animal in the 4 groups was given orally 0 (control), 10, 25 and 50ml/kg body weight of malathion, respectively. Chrysomya megacephala larvae were then allowed to grow on the liver of carcass. Larvae development was estimated by means of weight and length, time of adult emergence and survival rate. Results indicated that for the first 6 to 30 hours, larvae from control group developed more rapidly than larvae feeding on tissue containing malathion. However, the 3 doses of malathion did not exhibit significant impact on larvae length and weight. The time required for adult emergence was significantly greater for malathion-treated colony which was 10 days compared to 7 days in control colony. Control larvae of C. megacephala had higher survival rate compared to larvae exposed to the three different doses of malathion. Analysis of the tissues indicated that all rats and fly samples were positive for malathion. Malathion concentration was highest in liver. It was concluded that the presence of malathion altered the development rate of C. megacephala and thus disrupted normal postmortem interval estimation.
Circulating concentrations of endogenous compounds such as testosterone, complicate the analysis of pharmacokinetic parameters when these compounds are administered exogenously. This study examines the influence of three correction methods of accounting for endogenous concentrations on the determination of bioequivalence between two testosterone formulations.
Chemical inactivation of microorganisms is a common process widely employed in many fields such as in treatment of water, preservation in food industry and antimicrobial treatments in healthcare. For economy of applications and efficiency of treatment establishment the minimum dosage of breakpoint in the chemical application becomes essential. Even though experimental investigations have been extensive, theoretical understanding of such processes are demanding. Commonly employed theoretical analyses for the inactivation of microorganisms and depletion of chemicals include kinetics expressing the rates of depletion of chemical and microorganisms. The terms chemical demand (x) and specific disinfectant demand (alpha) are often used in theoretical modeling of inactivation. The value of specific disinfectant demand (alpha) has always been assumed to be a constant in these models. Intracellular concentration built up within the cells of the microorganisms during inactivation could lead to possible weakening effects of microorganisms thereby requiring lower doses as disinfection proceeds makes the assumption of constant alpha inaccurate. Model equations are formulated based on these observations co-relating the parameters alpha and x with a progressive inactivation (N/N(0)). The chemical concentration (C) is also presented in terms of the inactivation time (t) and the survival ratio (N/N(0)) for given pH and temperature conditions. The model is examined using experimentally verified Ct data of Giardia Cysts/chlorine system. The respective values of x for different survival ratios were evaluated from the data using MatLab software. Proposed model correlating for the disinfectant demand (x) with the survival ratio (N/N(0)) fits satisfactorily with those evaluated from data. The rate constants for different pH and temperature conditions are evaluated which showed compatibility with the Arrhenius model. The dependence of frequency factors with pH indicated compatibility with accepted models. The Ct values regenerated with the kinetic data shows a very accurate fit with published data.
Microspheres prepared from rigid guluronic acid- (MG) and flexible mannuronic acid-rich (MC) alginate will undergo different drug release changes with respect to the influence of microwave on the matrix. An in-depth understanding of their differences in drug release changes is attainable through investigating cross-linking agent-free alginate microspheres prepared by spray-drying technique.
Iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) combined with laser Doppler fluximetry (LDF) is a tool used to determine microvascular endothelial function. Our aim was to study the reproducibility of different parameters of this technique using iontophoresis with low current strength on the forearm skin of healthy subjects. Baseline skin perfusion was done before application of five current pulses with 1 min of current-free interval. Current strength of 0.007 mA, current density of 0.01 mA/cm(2) and charge density of 6 mC/cm(2) were used, along with 1% ACh and 1% SNP. The absolute maximum change in perfusion (max), percent change in perfusion (% change), peak change in perfusion (peak) and area under the curve during iontophoresis (AUC) at the anodal and cathodal leads were recorded. Measurements were performed in three sessions for 2 days. The coefficient of variation (CV) was calculated for each parameter. Among the parameters studied, maximum change in perfusion and peak flux were the most reproducible parameters.
Quantitation of isoflavones in humans is important to establish the benefits of these compounds to the populations. Urinary isoflavones are frequently used as a biomarker of isoflavone bioavailability from food or supplement since urine contains 100-fold higher concentrations of isoflavones. The objective of the present study was to determine and compare the urinary excretions of daidzein (DA), genistein (GE) and equol (EQ) in postmenopausal Malay women following the consumption of tempeh and milk in a calcium absorption study and to test the hypothesis that the excretion of isoflavones following consumption of tempeh maybe higher compared with milk. The amounts of DA (47.06 ± 4.18 μmol/h), GE (33.27 ± 3.71 μmol/h) and EQ (24.35 ± 4.34 μmol/h) excreted in urine following tempeh consumption were significantly higher (P < 0.05) compared with those in milk (3.51 ± 0.62 μmol/h DA, 2.79 ± 0.35 μmol/h GE and 0 μmol/h EQ). Almost all studied postmenopausal Malay women were able to excrete EQ following consumption of 240 g tempeh but only one subject can be classified as an equol producer. We concluded that most postmenopausal Malay women excreted DA, GE and EQ in their urine following tempeh consumption and the amount of the excreted isoflavones were higher compared with those in milk. However, further studies are needed to determine whether longer periods of time are required to capture EQ producers.
Tramadol is metabolized by the highly polymorphic enzyme cytochrome P450 (CYP)2D6. Patients with different CYP2D6 genotypes may respond differently to tramadol in terms of pain relief and adverse events. In this study, we compare the pharmacokinetics and effects of tramadol in Malaysian patients with different genotypes to establish the pharmacokinetic-pharmacodynamic relationship of tramadol.
Adult Macrobrachium lanchesteri were exposed for a 4-day period in laboratory conditions to a range of copper (Cu), cadmium (Cd), zinc (Zn) and lead (Pb) concentrations. Mortality was assessed and median lethal times (LT₅₀) and concentrations (LC₅₀) were calculated. At the end of the 4-day period, live prawns were used to determine bioconcentration of the metals. LT₅₀ and LC₅₀ increased with the decrease in mean exposure concentrations and times, respectively, for all metals. LC₅₀s for 96 hours for Cu, Cd, Zn and Pb were 32.3, 7.0, 525.1 and 35.0 µg/L, respectively. Cu, Cd, Zn and Pb bioconcentration in M. lanchesteri increases with exposure to increasing concentrations and Cd was the most toxic to M. lanchesteri, followed by Pb, Cu and Zn. Comparison of LC₅₀ values for metals for this species with those for other freshwater crustacean organisms reveals that M. lanchesteri is equally or more sensitive to heavy metals than most other tested crustaceans.
Matched MeSH terms: Water Pollutants, Chemical/pharmacokinetics; Metals, Heavy/pharmacokinetics
A simple validated LC-UV method for the phytochemical analysis of four bioactive quassinoids, 13alpha(21)-epoxyeurycomanone (EP), eurycomanone (EN), 13alpha,21-dihydroeurycomanone (ED) and eurycomanol (EL) in rat plasma following oral (200 mg/kg) and intravenous administration (10 mg/kg) of a standardized extract Fr 2 of Eurycoma longifolia Jack was developed for pharmacokinetic and bioavailability studies. The extract Fr 2 contained 4.0%, 18.5%, 0.7% and 9.5% of EP, EN, ED and EL, respectively. Following intravenous administration, EP displayed a relatively longer biological half-life (t1/2 = 0.75 +/- 0.25 h) due primarily to its lower elimination rate constant (k(e)) of 0.84 +/- 0.26 h(-1)) when compared with the t1/2 of 0.35 +/- 0.04 h and k(e) of 2.14 +/- 0.27 h(-1), respectively of EN. Following oral administration, EP showed a higher C(max) of 1.61 +/- 0.41 microg/mL over that of EN (C(max) = 0.53 +/- 0.10 microg/mL). The absolute bioavailability of EP was 9.5-fold higher than that of EN, not because of chemical degradation since both quassinoids were stable at the simulated gastric pH of 1. Instead, the higher log K(ow) value of EP (-0.43) contributed to greater membrane permeability over that of EN (log K(ow) = -1.46) at pH 1. In contrast, EL, being in higher concentration in the extract than EP, was not detected in the plasma after oral administration because of substantial degradation by the gastric juices after 2 h. Similarly, ED, being unstable at the acidic pH and together with its low concentration in Fr 2, was not detectable in the rat plasma. In conclusion, upon oral administration of the bioactive standardized extract Fr 2, EP and EN may be the only quassinoids contributing to the overall antimalarial activity; this is worthy of further investigation.
Fourth instars larvae of freshwater midge Chironomus javanus (Diptera, Chironomidae) were exposed for a 4-day period in laboratory conditions to a range of copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al) and manganese (Mn) concentrations. Mortality was assessed and median lethal concentrations (LC(50)) were calculated. LC(50) increased with the decrease in mean exposure times, for all metals. LC(50)s for 96 hours for Cu, Cd, Zn, Pb, Ni, Fe, Al and Mn were 0.17, 0.06, 5.57, 0.72, 5.32, 0.62, 1.43 and 5.27 mg/L, respectively. Metals bioconcentration in C. javanus increases with exposure to increasing concentrations and Cd was the most toxic to C. javanus, followed by Cu, Fe, Pb, Al, Mn, Zn and Ni (Cd > Cu > Fe > Pb > Al > Mn > Zn > Ni). Comparison of LC(50) values for metals for this species with those for other freshwater midges reveals that C. javanus is equally or more sensitive to metals than most other tested dipteran.
Matched MeSH terms: Metals/pharmacokinetics; Water Pollutants, Chemical/pharmacokinetics
A validated HPLC analysis of eurycomanone (1), a bioactive quassinoid, in rat plasma following oral and intravenous administration of Eurycoma longifolia Jack extract was developed for pharmacokinetic and bioavailability studies. Relatively high plasma eurycomanone concentrations were detected after an intravenous injection of 10 mg/kg extract F2 containing 1.96 mg/kg of the quassinoid. However, it declined rapidly to zero after 8 h. Its mean elimination rate constant (k(e)), biological half-life (t(1/2)), volume of distribution (V(d)) and clearance (CL) were 0.88 +/- 0.19 h (-1), 1.00 +/- 0.26 h, 0.68 +/- 0.30 L/kg and 0.39 +/- 0.08 L/h/kg, respectively. Following oral administration of eurycomanone, its Cmax and Tmax values were detected as 0.33 +/- 0.03 microg/mL and 4.40 +/- 0.98 h, respectively. The plasma concentration of the quassinoid after oral administration was much lower than after intravenous application in spite of the oral dose being 5 times higher. The results indicate that eurycomanone is poorly bioavailable when given orally. A comparison of the AUC (0-->infinity) obtained orally to that obtained after an intravenous administration (normalized for dose differences) revealed that the absolute bioavailability of the compound was low with 10.5 %. Furthermore, the compound appeared to be well distributed in the extravascular fluids because of its relatively high V(d) value. The poor oral bioavailability was not attributed to instability problems because eurycomanone has been shown to be stable under different pH conditions. Thus, its poor oral bioavailability may be due to poor membrane permeability in view of its low P value and/or high first-pass metabolism.
AIM: The bioequivalence of aspirin from two enteric-coated brands, Nu-seals and Loprin, identified as the reference (R) and test (T) products, respectively, was assessed.
METHODS: A two-period randomised crossover design with a washout interval of 15 days was used in this study. The study results were determined in 16 healthy volunteers, all males with ages ranging from 19-28 (23.33 +/- 3.74) years and bodyweights of 52-92 (65.89 +/- 11.39) kg. After oral ingestion of 150mg of the either brand with 200 mL of water, serial blood samples were obtained over a period of 24 hours. Plasma, harvested from blood was analysed for the concentration of salicylic acid, a deacetylated metabolite of aspirin, by a validated high performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were determined for both formulations by an interactive computer-assisted PK II procedure. A general linear model for repeated measures and 90% confidence intervals (CI) was employed to assess the sequence of treatment effects and to exclude differences between the parameters due to the product and period of administration, respectively.
RESULTS: The observed 90% CI ratios (Loprin/Nu-seals) for peak concentration, time to reach the peak and area under the plasma-concentration time curve from zero to infinity of 1.03,1.08; 1.04,1.05 and 1.01,1.15, respectively, were within the bioequivalence range (0.80,1.25) stipulated by the US Food and Drug Administration.
CONCLUSION: On the basis of the findings, the test (Loprin) and reference drug (Nu-seals) were deemed bioequivalent.
Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride.
Phenytoin has been reported to have major interactions with warfarin. Phenytoin induces warfarin's metabolism. However, there are many case reports which provide conflicting conclusions. Here, we report a case of a 65-year-old man with mechanical heart valve on chronic warfarin therapy who experienced persistent fluctuations of INR and bleeding secondary to probable warfarin-phenytoin interactions. The patient's anticoagulation clinic visits prior to hospitalization were thoroughly evaluated and we continued to follow-up the case for 3 months post-hospitalization. The reported interaction could be reasonably explained from the chronology of events and the pattern of INR fluctuations whenever phenytoin was either added or discontinued from his drug regimen.
The bioavailability of a generic diclofenac sodium sustained release tablet preparation (Zolterol, SR) was compared with the innovator product, Voltaren, SR. Twelve healthy adult male volunteers participated in the study, which was conducted according to a randomized, two-way crossover design with a wash out period of one week. The bioavailability of diclofenac was compared using the parameters area under the plasma concentration-time curve (AUC(0-infinity)), peak plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed for both logarithmically transformed AUC(0-infinity), Cmax values and Tmax value of the two preparations.
A bioequivalence study of two oral formulations of 500 mg tablets of ciprofloxacin (RAZA Pharmaniaga, Malaysia) as test and Ciprobay (Bayer AG, Germany) as reference, was carried out in 24 healthy human volunteers. Each volunteer received a single dose of ciprofloxacin.
Because of their magnetic properties, magnetic nanoparticles (MNPs) have numerous diverse biomedical applications. In addition, because of their ability to penetrate bacteria and biofilms, nanoantimicrobial agents have become increasingly popular for the control of infectious diseases. Here, MNPs were prepared through an iron salt coprecipitation method in an alkaline medium, followed by a chitosan coating step (CS-coated MNPs); finally, the MNPs were loaded with ampicillin (amp) to form an amp-CS-MNP nanocomposite. Both the MNPs and amp-CS-MNPs were subsequently characterized and evaluated for their antibacterial activity. X-ray diffraction results showed that the MNPs and nanocomposites were composed of pure magnetite. Fourier transform infrared spectra and thermogravimetric data for the MNPs, CS-coated MNPs, and amp-CS-MNP nanocomposite were compared, which confirmed the CS coating on the MNPs and the amp-loaded nanocomposite. Magnetization curves showed that both the MNPs and the amp-CS-MNP nanocomposites were superparamagnetic, with saturation magnetizations at 80.1 and 26.6 emu g(-1), respectively. Amp was loaded at 8.3%. Drug release was also studied, and the total release equilibrium for amp from the amp-CS-MNPs was 100% over 400 minutes. In addition, the antimicrobial activity of the amp-CS-MNP nanocomposite was determined using agar diffusion and growth inhibition assays against Gram-positive bacteria and Gram-negative bacteria, as well as Candida albicans. The minimum inhibitory concentration of the amp-CS-MNP nanocomposite was determined against bacteria including Mycobacterium tuberculosis. The synthesized nanocomposites exhibited antibacterial and antifungal properties, as well as antimycobacterial effects. Thus, this study introduces a novel β-lactam antibacterial-based nanocomposite that can decrease fungus activity on demand for numerous medical applications.
The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197-3207, 2015, http://dx.doi.org/10.1128/AAC.05013-14), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg · h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg · h/liter, respectively; P ≥ 0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick children before transfer for definitive management of severe or moderately severe malaria.