Different forms of copper Cu, zinc Zn, lead Pb and cadmium Cd in water from the Uganda side of Lake Victoria (25°C, pH 6.75-7.18), the second largest inland freshwater lake in the world, have been ...studied using ion-exchange, dialysis and atomic absorption spectrophotometry. The results indicate that heavy metals Cu, Zn, Pb and Cd are present mainly in the cationic form (80-83%). Small quantities of anionic (13-22%), non-ionic, dialyzable (4-8%), and non-ionic, non-dialyzable (< 1.3-4.4%) forms were also detected for all metals except Cd. The corresponding concentrations lay in the ranges: cationic, 0.06-0.99; anionic, < 0.001-0.25; non-ionic, dialyzable, < 0.001-0.08; non-ionic, non-dialyzable, < 0.001-0.06 µg ml
−1
. The existence of the metals in non-ionic and non-dialyzable forms is attributable to metal associations with high relative molecular mass (RMM) organic matters.
A pre-packaged fixed-dose formulation of chloroquine (CQ) and sulfadoxine/pyrimethamine (S/P) combination (Homapak) is widely used for the treatment of falciparum malaria in Ugandan children. It is ...however a product whose pharmacokinetics and interactions have not been studied.
To explore possible pharmacokinetic interactions between CQ and S/P during co-administration, and to determine their bioavailability in the locally made Homapak compared to the Good Manufacturing Practice (GMP) made formulations.
Thirty-two adult healthy volunteers were randomized into four groups and given single oral doses of fixed-dose CQ+S/P combination (Homapak), or GMP formulations of S/P (Fansidar), CQ (Pharco), or their combination. Plasma samples were followed for 21 days, analysed by HPLC-UV methods, with pharmacokinetic modeling using the WinNonlin software.
Sulfadoxine in Homapak was more rapidly absorbed (ka = 0.55 h(-1)) than in Fansidar + CQ (ka = 0.27 h(-1), p=0.004), but not more than S in Fansidar alone group (ka = 0.32 h(-1), p=0.03). No significant differences were observed in the other pharmacokinetic parameters of S, P and CQ when given together or separately. The relative bioavailability of CQ and S in Homapak showed bioequivalence to reference formulations.
There were no pharmacokinetic interactions between CQ, S and P when the compounds were given together, however, more investigations would be needed to explore this further. Compared with GMP made drugs, both S and CQ are bioequivalent in Homapak, the Ugandan made fixed-dose formulation. Furthermore, the absorption of S was more rapid which could be advantageous in malaria treatment.
Malaria in pregnancy is a major health problem that can cause maternal anaemia, stillbirth, spontaneous abortion, low birth weight and intra-uterine stunting. The WHO recommends use of ...sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy (IPTp) in endemic areas. Towards monitoring and assessing IPTp coverage in the population, the Roll Back Malaria Partnership recommends the use of self-reported data. The aim of this study was to assess the validity of self-reported IPTp by testing for sulphadoxine in maternal blood at delivery.
Two hundred and four pregnant women were consented and enrolled in a cross-sectional study in Mulago National Referral Hospital in Kampala Uganda. - Participants who reported a history of taking sulpha-containing drugs like co-trimoxazole , those who were not sure of dates relating to last menstrual period or who took IPTp within the first 20 weeks of gestation were excluded from the study. Data on demographic characteristics, obstetric history, and delivery outcome were collected. At birth, maternal venous blood was taken off aseptically and used to make thick blood smears for malaria parasites and plasma for determining sulphadoxine using high performance liquid chromatography (HPLC).
Of 120 participants who self reported to have used IPTp, 35 (29.2%) tested positive for sulphadoxine by HPLC, while 63 (75%) of 84 patients who reported not having used IPTp tested negative for sulphadoxine. Participants possessing post-primary education were more likely to have reported using IPTp. The low agreement (kappa coefficient = 0.037) between self-report and actual presence of the drug in the blood casts doubt on the validity of self-reported data in estimating IPTp coverage.
The results of this study question the accuracy of self-reported data in estimating IPTp coverage in the population. More studies on validity of self reported data are recommended. Since the validity of IPTp self reports is vital for guiding policy on malaria control in pregnancy, ways should be sought to improve accuracy of the information from such reports.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study has been done with the objective of knowing more about the Anopheles evolutions situation at Lwiro-Katana from 1967 up to 2014. On seven species identified in this region, only four were ...permanent in nine investigations done. The geometric average calculated shows the evolution of 3.152 for Anopheles funestus, 2.867 for An. gambiae, 2.663 for An. demeilloni and 2.441 for An. marshallii. These species share almost the same ecological conditions for their larval development found in different kinds of water. These conditions were created by the anthropisation of the region followed by some activities. The increasing process attests that An. funestus, An. gambiae and An. demeilloni have an increasing tendency while An. marshallii has a decreasing tendency and is likely to approach the 0 level. An. coustani and An. christyi miss the stability development due to the environmental pertubations since 1980 in this environment. An. kingi wasn't identified after 1980. All of these species of anopheles share the same ecological niche and present a scientific interest. The knowledge of their evolution in this area is really very important because it helps to have better vector control. Also three of those mosquitos (An. gambiae, An. funestus and An. marshallii) are the greatest responsible of the killing paludism South of the Sahara.
Co‐administration of artemether–lumefantrine with milk is recommended to improve lumefantrine (L) absorption but milk may not be available in resource‐limited settings. This study explored the ...effects of cheap local food in Uganda on oral bioavailability of lumefantrine relative to milk. In an open‐label, four‐period crossover study, 13 healthy adult volunteers were randomized to receive a single oral dose of artemether–lumefantrine (80 mg artemether/480 mg lumefantrine) with water, milk, maize porridge or maize porridge with oil on separate occasions. Plasma lumefantrine was assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic exposure parameters were determined by non‐compartmental methods using WinNonlin. Peak concentrations (Cmax) and area under concentration–time curve restricted to 48 hr after single dosing (AUC(0–48)) were selected for relative bioavailability evaluations using confidence interval approach for average bioequivalence. Lumefantrine exposure was comparable in milk and maize porridge plus oil study groups. When artemether–lumefantrine was administered with maize porridge plus oil, average bioequivalence ranges (means ratios 90% CI, 0.84–1.88 and 0.85–1.69 for Cmax and AUC(0–48), respectively) were within and exceeded acceptance ranges relative to milk (90% CI, 0.80–1.25). Both fasted and maize porridge groups demonstrated similarly much lower ranges of lumefantrine exposures (bioinequivalence) relative to milk. If milk is not available, it is thus possible to recommend fortification of carbohydrate‐rich food with little fat (maize porridge plus vegetable oil) to achieve similarly optimal absorption of lumefantrine after artemether–lumefantrine administration.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Both chloroquine (CQ) and sulfadoxine/ pyrimethamine (SDx/PYR) remain important drugs in the control of malaria.
• The available data on CQ, SDx and PYR are ...summary pharmacokinetic parameters based on classical/traditional methods, mostly in adults.
• No study has described the population pharmacokinetics of a fixed‐dose CQ + SDx/PYR combination in children with falciparum malaria.
WHAT THIS STUDY ADDS
• This study presents population pharmacokinetic data on CQ and SDx in children with uncomplicated falciparum malaria.
• The study demonstrates that in age‐based fixed‐dose regimens with CQ and SDx, drug exposures and outcomes may be correctly predicted, although correlation with body weight is poor.
• The study proposes dose modification to improve response with the CQ + SDx/PYR combination.
AIMS
To describe the pharmacokinetics of chloroquine (CQ) and sulfadoxine (SDx), and to identify predictors of treatment response in children with malaria given the CQ + SDx and pyrimethamine (PYR) combination.
METHODS
Eighty‐six Ugandan children with uncomplicated falciparum malaria, 6 months to 5 years old, were randomly treated with prepacked fixed‐dose CQ + SDx/PYR. The youngest children (<24 months) received half strength and the older (>24 months) full strength treatment. The reported day 14 failure rates were 48% and 18%, respectively. Capillary blood (100 μl) applied on to filter paper was collected on eight occasions during 28 days of follow up. Concentrations of CQ and SDx were determined. A population approach was used for the pharmacokinetic analysis.
RESULTS
A two‐compartment model adequately described the data for both CQ and SDx. For CQ, the typical apparent clearance (CL/F) and volume of distribution (VC/F) values were estimated to be 2.84 l h−1 and 230 l. The typical CL/F for SDx was 0.023 l h−1, while the factor relating its VC/F to normalized body weight was 1.6 l kg−1. Post hoc parameter estimates for both drugs showed lower maximum concentrations (Cmax) and concentration‐time curve areas (AUC(0,336 h)) in younger children. The AUC(0,336 h) for SDx and CQ were independently significant factors for prediction of cure. Simulations suggest that giving the higher dose to the youngest children would result in higher CQ and SDx concentrations and improved outcome.
CONCLUSIONS
The study results suggest that full‐strength combination to all children would improve the cure rate.
Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative ...first-line regimen to Coartem(R) (artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper.
Twelve patients aged between 1.5 to 8 years with uncomplicated malaria received three standard oral doses of AQ+AS. Filter paper blood samples were collected before drug intake and at six different time points over 28 days period. A new field-adapted sampling procedure and liquid chromatographic method was used for quantitative determination of amodiaquine and its metabolite in whole blood.
The sampling procedure was successively applied in the field. Amodiaquine could be quantified for at least three days and the metabolite up to 28 days. All parasites in all the 12 patients cleared within the first three days of treatment and no adverse drug effects were observed.
The methodology is suitable for field studies. The possibility to determine the concentration of the active metabolite of amodiaquine up to 28 days suggested that the method is sensitive enough to monitor amodiaquine utilization in patients. Amodiaquine plus artesunate seems effective for treatment of falciparum malaria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A study of inorganic complexation of lead using drop amalgam voltammetry is described. The study has been carried out in simulated salt lake water and at ionic strength of 7.35 M, the predetermined ...ionic strength of Lake Katwe. The complexation of lead with the simple ligands (Cl-, CO32-) created anodic waves and the shifts of the peak potentials of lead with the introduction of varying concentrations of each ligand measured. The analysis of these shifts furnished information about the stability constants of the lead complexes which was employed in the calculation of lead species distribution. These mathematical treatments revealed the existence of two lead chloride complexes with corresponding stability constants log beta sub( 1) = 0.88, log beta sub( 2) = 2.95; and two carbonate complexes with log beta sub( 1) = 8.50 and log beta sub( 2) = 9.62. The results obtained indicate that in Lake Katwe water (25 sub(o) C, carbonate alkalinity = 0.11 M, pH 11) approximately 0.00% of total inorganic lead exists as the free ion, and at chloride concentration of 1.8 M only 1.3% of lead exists as the free ion.
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