Copper biodistribution after acute systemic administration of copper gluconate to rats.

Neurodegenerative disorders have been linked to the decrease of copper concentrations in different regions of the brain. Therefore, intake of micronutrient supplements could be a therapeutic alternative. Since the copper distribution profile has not been elucidated yet, the aim of this study was to characterize and to analyze the concentration profile of a single administration of copper gluconate to rats by two routes of administration. Male Wistar rats were divided into three groups. The control group received vehicle (n = 5), and the experimental groups received 79.5 mg/kg of copper orally (n = 4-6) or 0.64 mg/kg of copper intravenously. (n = 3-4). Blood, striatum, midbrain and liver samples were collected at different times. Copper concentrations were assessed using atomic absorption spectrophotometry. Copper concentration in samples from the control group were considered as baseline. The highest copper concentration in plasma was observed at 1.5 h after oral administration, while copper was quickly compartmentalized within the first hour after intravenous administration. The striatum evidenced a maximum metal concentration at 0.25 h for both routes of administration, however, the midbrain did not show any change. The highest concentration of the metal was held by the liver. The use of copper salts as replacement therapy should consider its rapid and discrete accumulation into the brain and the rapid and massive distribution of the metal into the liver for both oral and intravenous routes. Development of controlled-release pharmaceutical formulations may overcome the problems that the liver accumulation may imply, particularly, for hepatic copper toxicity.

Retrograde transport of radiolabelled botulinum neurotoxin type A to the CNS after intradetrusor injection in rats.

OBJECTIVE: To investigate the potential distribution of radiolabelled botulinum neurotoxin type A (BoNT/A) in the CNS after bladder injection in normal rats, by using the gamma-emitting radionuclide technetium-99 m ((99m) Tc). MATERIALS AND METHODS: BoNT/A was radiolabelled by pretreatment with 2-iminothiolane and incubation with (99m) Tc-gluconate. The labelled toxin (99m) Tc-BoNT/A was purified using size exclusion HPLC. Twenty-four female Wistar rats were evenly injected in the bladder wall with either (99m) Tc-ΒοΝΤ/Α (n = 12) or free (99m) Tc (n = 12). Four rats from each group were killed at 1, 3 and 6 h after injection, respectively. The bladder, L6-S1 spinal cord segment and L6-S1 dorsal root ganglia (DRG) were harvested and their radioactivity counted in a gamma scintillation detector. Results were calculated as % injected dose (I.D.) per gram of tissue. The paired t-test was used for comparison of means of (99m) Tc-ΒοΝΤ/Α radioactivity vs free (99m) Tc in the tissues of interest. RESULTS: Radiolabelled BoNT/A had a high radiochemical stability of 70% after 24 h. Gradual accumulation of (99m) Tc-ΒοΝΤ/Α was observed in the DRG up to 6 h after injection (P = 0.04 and P = 0.029 compared with 1 h and 3 h, respectively), while no accumulation was detected for free (99m) Tc. Consequently, (99m) Tc-ΒοΝΤ/Α radioactivity in the DRG was higher than free (99m) Tc radioactivity (3.18 ± 0.67% I.D./g vs 0.19 ± 0.10% I.D./g [P = 0.002] 6 h after injection). Values for (99m) Tc-ΒοΝΤ/Α radioactivity in the spinal cord were higher than those for free (99m) Tc, but not significantly. The bladder retained higher dosages of (99m) Tc-ΒοΝΤ/Α than free (99m) Tc at all time points. CONCLUSIONS: Significant accumulation of the radiolabelled toxin in the lumbosacral DRG, together with a less significant uptake in the respective spinal cord segment as opposed to free radioactivity provide first evidence of the retrograde transport of BoNT/A to the CNS after bladder injection in rats.

Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide.

The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with (67)Zn and (70)Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6-71.0) and was not different from that from zinc gluconate with 60.9% (50.6-71.7). Absorption from zinc oxide at 49.9% (40.9-57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627.

The bioavailability of different zinc compounds used as human dietary supplements in rat prostate: a comparative study.

The normal human prostate accumulates the highest levels of zinc (Zn) of any soft tissue in the body. The pool of zinc available to the body is known to significantly decrease with age. It is suggested that dietary Zn supplementation protects against oxidative damage and reduces the risk of cancer. Zinc sulfate and zinc gluconate were the most frequently mentioned in per os administration in studies on Zn supplementation. The major aim of the study was to compare the bioavailability of different Zn compounds (sulfate, gluconate and citrate) in the prostate after their daily administration to male rats at three different doses (3.0; 15.0; and 50.0 mg Zn/kg b.w.) for 30 days. The results show that bioavailability in the prostate differs significantly between individual zinc preparations. A significantly elevated Zn concentration in the dorso-lateral lobe of the prostate, compared to controls, was found in the rats supplemented with two compounds only: zinc gluconate and zinc citrate. However, after administration of zinc gluconate, this effect occurred even at the lowest dose. The lowest zinc bioavailability in the prostate was found in the rats administered zinc sulfate: no significant Zn increase was seen in particular zones of the prostate. To sum up, the use of zinc gluconate is worth considering as a possible means of zinc supplementation in men.

Mn bioavailability by polarized Caco-2 cells: comparison between Mn gluconate and Mn oxyprolinate.

BACKGROUND: Micronutrient inadequate intake is responsible of pathological deficiencies and there is a need of assessing the effectiveness of metal supplementation, frequently proposed to rebalance poor diets. Manganese (Mn) is present in many enzymatic intracellular systems crucial for the regulation of cell metabolism, and is contained in commercially available metal supplements. METHODS: We compared the effects of two different commercial Mn forms, gluconate (MnGluc) and oxyprolinate (MnOxP). For this purpose we used the polarized Caco-2 cells cultured on transwell filters, an established in vitro model of intestinal epithelium. Since micronutrient deficiency may accelerate mitochondrial efficiency, the mitochondrial response of these cells, in the presence of MnGluc and MnOxP, by microscopy methods and by ATP luminescence assay was used. RESULTS: In the presence of both MnOxP and MnGluc a sustained mitochondrial activity was shown by mitoTraker labeling (indicative of mitochondrial respiration), but ATP intracellular content remained comparable to untreated cells only in the presence of MnOxP. In addition MnOxP transiently up-regulated the antioxidant enzyme Mn superoxide dismutase more efficiently than MnGluc. Both metal treatments preserved NADH and ßNADPH diaphorase oxidative activity, avoided mitochondrial dysfunction, as assessed by the absence of a sustained phosphoERK activation, and were able to maintain cell viability. CONCLUSIONS: Collectively, our data indicate that MnOxP and MnGluc, and primarily the former, produce a moderate and safe modification of Caco-2 cell metabolism, by activating positive enzymatic mechanisms, thus could contribute to long-term maintenance of cell homeostasis.

Dietary management of hepatic copper accumulation in Labrador Retrievers.

BACKGROUND: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases. OBJECTIVES: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations. ANIMALS: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations. METHODS: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo. RESULTS: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P= .001) and at recheck 2 (n= 16; group 1, P= .03; group 2, P= .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment (P= .65), at recheck 1 or at recheck 2 (P= .52-.79). CONCLUSIONS AND CLINICAL RELEVANCE: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.

Clinical evaluation of the bioavailability of zinc-enriched yeast and zinc gluconate in healthy volunteers.

Zinc (Zn)-enriched yeast and gluconate are considered two of the more biologically available supplements. However, there have been few reports comparing the bioavailability of these supplements. The objective of this study was to demonstrate whether Zn was absorbed better by healthy male volunteers when given supplements where the mineral is found organically bound in yeast or as a salt gluconate form. The trial used a randomized, two-way crossover design. Urine, blood, and fecal samples were collected and analyzed over a 48-h period after a single dose of supplement. The net Zn balance and the relative bioavailability were calculated. No differences were observed in urine excretion of the two supplements. Zinc gluconate gave higher Zn concentrations in the blood in the first 6 h but also showed greater losses in the feces. Zinc yeast also increased in blood with time but showed significantly less loss in the feces. Thus, the net Zn balance after 48 h for Zn yeast was 9.46 but for Zn gluconate it was -2.00, indicating that Zn gluconate supplementation contributed to a net loss of Zn. It was concluded that organic Zn yeast supplements are more biologically available than Zn gluconate salts.

Comparative bioavailability of mineral-enriched gluconates and yeast in rat liver after depletion-repletion feeding.

There are many forms of mineral supplements currently available. Among these mineral-enriched gluconates and yeast are considered two of the more biologically available supplements. The purpose of this study was to use zinc (Zn)- or copper (Cu)-deficient rats to determine whether the organically bound mineral in yeast or the salt gluconate form was more bioavailable, i.e., is absorbed and found in a greater concentration in liver. It was demonstrated that Zn-enriched yeast was 3.7 times more bioavailable than the Zn gluconate and that Cu-enriched yeast was 1.4 times more bioavailable than the Cu gluconate.

A bioavailability study comparing two oral formulations containing zinc (Zn bis-glycinate vs. Zn gluconate) after a single administration to twelve healthy female volunteers.

As the current nutritional zinc intake frequently falls outside the Dietary Reference Intake (DRI) and as zinc is an essential trace mineral involved in the function of many enzymes, zinc supplementation has been recommended to prevent or treat the adverse effects of zinc deficiency. The aim of the present study was to compare the oral bioavailability of zinc bis-glycinate (a new formulation) with zinc gluconate (reference formulation). A randomized, cross-over study was conducted in 12 female volunteers. The two products were administrated orally at the single dose of 15 mg (7.5 mg x 2), with a 7-day wash-out period between the two tests. Serum concentrations of zinc were assayed by a validated inductively coupled plasma optical emission spectrometry (ICP-OES) method and C(max), T(max), and areas-under-the-curve (AUCs) were determined. The comparison between the two treatments was performed by comparing the C(max), AUC(t), and AUC(inf) using an analysis of variance followed by the calculation of the 90% confidence intervals of the ratio test/reference. Bis-glycinate administration was safe and well tolerated and bis-glycinate significantly increased the oral bioavailability of zinc (+43.4%) compared with the gluconate.

The Effect of Zinc Supplementation on Expressed Levels of Peroxisome Proliferator-Activated Receptor Gamma and Glucose Transporter Type 1 Genes in Newborns of Women with Gestational Diabetes Mellitus.

The current study was designed to determine the beneficial effects of zinc supplementation on expressed levels of peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucose transporter type 1 (GLUT1) genes in newborns of women with gestational diabetes mellitus (GDM). This randomized, double-blind, placebo-controlled clinical trial was performed among 40 women with GDM. Patients were randomly allocated to intake either 233 mg zinc gluconate (containing 30 mg zinc) (n = 20) or a placebo (n = 20) for 6 weeks. PPAR-γ and GLUT1 mRNA levels were quantified in umbilical cord blood of newborns of women with GDM. After 6 weeks of intervention, the change in serum zinc levels was greater in women consuming zinc than in the placebo group (+11.1 ± 13.4 vs. -4.8 ± 17.3 mg/dL, P = 0.002). Quantitative results of RT-PCR demonstrated that compared with the placebo, zinc supplementation resulted in a significant increase of expressed levels of PPAR-γ mRNA (P < 0.001) and GLUT1 mRNA (P < 0.001) in umbilical cord blood of newborns of women with GDM. Taken together, the current study demonstrated that zinc supplementation for 6 weeks among GDM women increased the mRNA levels of PPAR-γ and GLUT1 in their newborns compared with the placebo group.

Pharmacokinetic and Toxicological Evaluation of a Zinc Gluconate-Based Chemical Sterilant Using In Vitro and In Silico Approaches.

Sclerosing agents as zinc gluconate-based chemical sterilants (Infertile®) are used for chemical castration. This solution is injected into the animal testis, but there are not enough evidences of its safety profiles for the receivers. The present work aimed to establish the pharmacokinetics and toxicological activity of Infertile, using in vitro and in silico approaches. The evaluation at the endpoint showed effects in a dose-dependent manner. Since necrosis is potentially carcinogenic, the possible cell death mechanism could be apoptosis. Our data suggested that Infertile at 60 mM presented risk for animal health. Even though Infertile is a licensed product by the Brazilian Ministry of Agriculture, Livestock and Supply, it presented a high mutagenic potential. We suggest that the optimal dose must be less than 6 mM, once, at this concentration, no mutagenicity or genotoxicity was observed.

The Effect of Zinc and Selenium Supplementation Mode on Their Bioavailability in the Rat Prostate. Should Administration Be Joint or Separate?

It is thought that zinc and selenium deficiency may play a significant role in the etiology of prostate cancer. Although joint zinc and selenium supplementation is frequently applied in the prevention of prostate diseases, the bioavailability of these elements in the prostate after co-administration is still unknown. The study examines the effect of subchronic supplementation of zinc gluconate and selenium compounds (sodium selenite or selenomethionine), administered together or separately, on their bioavailability in the prostate, as well as the induction of metallothionein-like proteins (MTs) bound to zinc in the prostate and liver. Zinc concentration in the dorso-lateral lobe of the prostate was significantly elevated already after the first month of supplementation of zinc alone. In the supplementation period, the MTs level increased together with zinc concentration. In contrast, the ventral lobe of the prostate did not demonstrate significantly higher levels of zinc until after three months of supplementation, despite the MTs induction noted after one-month supplementation. Increased selenium levels in the dorsolateral lobe were observed throughout the administration and post-administration periods, regardless of the selenium compound used or whether zinc was co-administered. The results of our studies suggested for the first time that these elements should not be administered jointly in supplementation.

Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial.

BACKGROUND: The bioavailability of potassium should be considered in setting requirements, but to our knowledge, the bioavailability from individual foods has not been determined. Potatoes provide 19-20% of potassium in the American diet. OBJECTIVE: We compared the bioavailability and dose response of potassium from nonfried white potatoes with skin [targeted at 20, 40, and 60 milliequivalents (mEq) K] and French fries (40 mEq K) with potassium gluconate at the same doses when added to a basal diet that contained ∼60 mEq K. DESIGN: Thirty-five healthy, normotensive men and women with a mean ± SD age of 29.7 ± 11.2 y and body mass index (in kg/m(2)) of 24.3 ± 4.4 were enrolled in a single-blind, crossover, randomized controlled trial. Participants were partially randomly assigned to the order of testing for nine 5-d interventions of additional potassium as follows: 0 (control; repeated at phases 1 and 5), 20, 40, and 60 mEq K/d consumed as a potassium gluconate supplement or as unfried potato or 40 mEq K from French fries completed at phase 9. The bioavailability of potassium was determined from the area under the curve (AUC) of serial blood draws and cumulative urinary excretion during a 24-h period and from a kinetic analysis. The effects of the potassium source and dose on the change in blood pressure and augmentation index (AIx) were determined. RESULTS: The serum potassium AUC increased with the dose (P < 0.0001) and did not differ because of the source (P = 0.53). Cumulative 24-h urinary potassium also increased with the dose (P < 0.0001) and was greater with the potato than with the supplement (P < 0.0001). The kinetic analysis showed the absorption efficiency was high across all interventions (>94% ± 12%). There were no significant differences in the change in blood pressure or AIx with the treatment source or dose. CONCLUSIONS: The bioavailability of potassium is as high from potatoes as from potassium gluconate supplements. Future studies that measure the effect of dietary potassium on blood pressure will need to evaluate the effect of various dietary sources on potassium retention and in both normal and hypertensive populations. This trial was registered at clinicaltrials.gov as NCT01881295.

Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands.

AIM: To study the accumulation and washout kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilic P-glycoprotein ligands. METHODS: The tumour cells were incubated in the presence and absence of the ligands and the uptakes of 99mTc-MIBI, rhodamine 123 and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) were measured. RESULTS: The accumulation of 99mTc-MIBI in the tumour cells followed biphasic kinetics. Verapamil and cyclosporin A increased the membrane fluidity and significantly enhanced the 99mTc-MIBI uptake of the MDR negative cells, while the rhodamine 123 uptake was not affected. Verapamil significantly increased the uptake of rhodamine 123 and 18FDG but did not modify that of 99mTc-MIBI in the MDR positive cells. Cyclosporin A significantly increased the 18FDG uptake of the MDR positive and negative tumour cells; these effects were ouabain-sensitive. Depolarization of the cytoplasmic membrane, acidification of the extracellular medium and the administration of CCCP decreased the accumulation of 99mTc-MIBI and rhodamine 123 uptake in the tumour cells. CONCLUSIONS: Lipophilic P-glycoprotein ligands modified the biphasic accumulation kinetics of the 99mTc-MIBI uptakes of MDR negative and positive tumour cells in different and complex ways and could therefore mask the P-glycoprotein pump-dependent changes in tracer accumulation.

The pharmacokinetics of zinc from zinc gluconate: a comparison with zinc oxide in healthy men.

OBJECTIVE: Zinc supplementation is beneficial in some clinical conditions such as age-related macula degeneration (AMD). It has been suggested that zinc absorption is influenced by the form in which zinc is ingested. Therefore, the pharmacokinetics of zinc gluconate (organic) were compared with those of zinc oxide (inorganic). METHODS: 12 healthy male subjects aged between 21 and 31 years (24 years median) orally received daily doses of 20 mg metal zinc as zinc gluconate and 17.4 mg metal zinc as zinc oxide under randomized crossover conditions for 14 days each with at least 14 days as a washout. Zinc plasma concentrations were measured by means of inductively coupled plasma-atomic emission spectroscopy. RESULTS: C(max) was found 18.3% (10.3 - 26.3%) higher following multiple-dose administration of zinc gluconate as compared to zinc oxide (mean; 0.95% confidence interval of the relative differences between both treatment conditions; p < 0.05). AUC(0-24h) was noted 8.1% (1.9 - 14.3%) higher after zinc was given as zinc gluconate when compared to zinc oxide (p < 0.05) whereas t(max) did not differ between both treatment conditions. CONCLUSIONS: Zinc absorption in humans could be improved by zinc complexation with gluconate.

Effect of hypoxia on the accumulation of technetium-99m-glucarate and technetium-99m-gluconate by Chinese hamster ovary cells in vitro.

The accumulation of 99mTc-glucarate, an agent recently reported to localize in acutely infarcted myocardium, zones of acute cerebral injury and tumors, has been compared with 99mTc-gluconate in an in vitro system of cultured Chinese hamster ovary fibroblasts. The effects on accumulation of hypoxia and competition with fructose have been studied. Both labeled glucose analogs showed a two- to threefold enhanced accumulation in hypoxic cells relative to aerobic cells. No such enhanced accumulation under hypoxia was observed for the nonsugar tracers pertechnetate and 99mTc-DTPA. The presence of 20 mM fructose reduced the accumulation of 99mTc-glucarate by 30% (p = 0.067) and 99mTc-gluconate by 40% (p < 0.05) in hypoxic cells, but had no significant effect in aerobic cells. These results suggest that both compounds at least partially share a common mechanism of uptake and/or accumulation with fructose.

An experimental model system for leishmaniasis. An ultrastructural study on cultured macrophages exposed to Leishmania parasites and sodium stibogluconate.

To facilitate studies on the effect of chemotherapeutic agents on the host-parasite interaction in leishmaniasis, we have developed an experimental model for infecting mouse peritoneal macrophages in culture with recently-isolated Leishmania donovani promastigotes. As the drug action is often dependent on concentration, the distribution of sodium stibogluconate, which is the commonly used drug for treatment of leishmaniasis, was studied in various parts of the macrophages by energy dispersive X-ray microanalysis. The drug was found to accumulate in secondary lysosomes. The ultrastructural examination, using TEM and SEM, of macrophages, whose secondary lysosomes had been preloaded with gold particles, showed that leishmania parasites are phagocytosed and finally located in secondary lysosomes. Using flameless atomic absorption spectrophotometry, the concentration of Mn, Fe and Cu in promastigotes of Leishmania donovani, Leishmania aethiopica, Leishmania crithidia, Leishmania major and their culture media was estimated. Of the three transition metals, the parasites accumulated only Mn from the medium, which they may use in a primitive defense mechanism against reactive oxygen metabolites produced by macrophages during the respiratory burst associated with phagocytosis.

Pharmacokinetics of pentavalent antimony (Pentostam) in hamsters.

Pentavalent antimony (Sb) is the classical treatment for visceral and cutaneous leishmaniasis. We investigated Sb levels in serum, liver, spleen, and skin of hamsters administered therapeutic dosages of Sb (600 and 300 mg Sb/kg). Single administration of Sb was more effective against hepatic parasites than dividing the same total dose into multiple administrations, which suggests that for elimination of hepatic parasites in vivo, peak Sb concentration is more important than total area-under-the-curve levels. Serum Sb declined with an initial half-life of 1 hr. Skin Sb levels (352 micrograms Sb/g 1 hr after 600 mg Sb/kg) were initially higher than liver levels (77 micrograms Sb/g) or splenic levels (156 micrograms Sb/g), but levels were comparable (7-24 micrograms Sb/g) in the three organs by 8 hr after dosing. The generally comparable levels of Sb in the skin and in the visceral organs support the present clinical practice of administering the same dosage of Sb for cutaneous and visceral leishmaniasis.

Blood and urinary magnesium kinetics after oral magnesium supplements.

A study was conducted to compare the pharmacokinetic profile of three oral magnesium supplements--magnesium chloride solution, slow-release magnesium chloride tablets, and magnesium gluconate tablets--at 16 mmol/dose. Twelve healthy normomagnesemic subjects were evaluated during an initial baseline study, followed by three magnesium supplementation studies. Supplements were administered in a randomized, crossover fashion at weekly intervals. During each of the four trials, subjects followed the same routines and consumed identical diets. Magnesium concentrations were measured in urine samples collected from 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours. Intraleukocyte, total serum, and ultrafiltrable magnesium were measured in blood samples drawn at 0, 1, 2, 3, 4, 8, 12, and 24 hours. Compared with baseline, 24-hour urinary magnesium excretion significantly increased (P < 0.05) after the administration of the magnesium chloride solution and also increased after the administration of the other supplements, but the difference was not significant. The 24-hour areas under the curve (AUCs) for total serum, ultrafiltrable, and leukocyte magnesium were greater after the administration of each of the supplements when compared with baseline, although the differences were not statistically significant. Differences in delta AUCs (supplement AUC minus baseline AUC) for total magnesium, ultrafiltrable magnesium, and 24-hour urinary magnesium excretion were statistically different from zero or between supplements. Statistically significant differences (P < 0.05) in total serum, ultrafiltrable, and leukocyte magnesium concentrations were observed at various time points. These results suggest that there were no major differences in the overall effect of these supplements on total serum, ultrafiltrable, and leukocyte magnesium concentrations but do reveal differences in the time-concentration profiles in magnesium levels in blood and urine among the three supplement forms.

Pharmacokinetics of antimony during treatment of visceral leishmaniasis with sodium stibogluconate or meglumine antimoniate.

5 patients with visceral leishmaniasis were treated with sodium stibogluconate (2 patients) or meglumine antimoniate (3 patients) given intramuscularly at a dose of 10 mg antimony (Sb) per kg body weight daily for 30 d. Blood samples were obtained at intervals during treatment and blood Sb concentrations measured by anodic stripping voltametry. The pharmacokinetics of both drugs were remarkably similar, with peak concentrations of approximately 10 mg/litre occurring 2 h after the initial dose. Most of the Sb was eliminated rapidly, but nadir Sb concentrations increased gradually during treatment from 0.04-0.08 mg/litre 24 h after the first dose to 0.19-0.33 mg/litre 24 h after the 30th dose. For both drugs, the data were best described by a two compartment, three term pharmacokinetic model representing an initial absorption phase with a mean half-life of 0.85 h, a rapid elimination phase with a mean half-life of 2.02 h, and a slow elimination phase with a mean half-life of 76 h. The slow terminal elimination phase may be related to in vivo conversion of pentavalent Sb to trivalent Sb, which could contribute to the toxicity associated with long-term high dose therapy.