Renal Clearance of Pentavalent Antimony (Sodium Stibogluconate)

Rees, Philip; Kager, P. A.; Keating, M.I.; Hockmeyer, Wayne T.

doi:10.1016/s0140-6736(80)90120-8

Cited by 121 publications

(44 citation statements)

References 4 publications

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“…Similar results have been reported for dogs treated with meglumine antimoniate (4,33) and human patients given antimonial drugs (10,16,25,27). The short t 1/2␤ s obtained in this study for dogs given SSG solution (t 1/2␤ s, 71.1 Ϯ 18.4 min for 10 mg of Sb V /kg and 88 Ϯ 31 min for 40 mg of Sb V /kg) are also indicative of rapid clearance of the drug.…”

Section: Discussionsupporting

confidence: 88%

“…The short t 1/2␤ s obtained in this study for dogs given SSG solution (t 1/2␤ s, 71.1 Ϯ 18.4 min for 10 mg of Sb V /kg and 88 Ϯ 31 min for 40 mg of Sb V /kg) are also indicative of rapid clearance of the drug. The main route of excretion for antimonial drugs is via the kidney (16,27); therefore, the glomerular filtration rate influences how fast the drug can be cleared from the systemic circulation postdosing. In this study the calculated clearance rate for SSG solution is within the normal range for the glomerular filtration rate in the dog (24).…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics, Toxicities, and Efficacies of Sodium Stibogluconate Formulations after Intravenous Administration in Animals

Nieto

Alvar

Mullen³

et al. 2003

Antimicrob Agents Chemother

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, Toxicities, and Efficacies of Sodium Stibogluconate Formulations after Intravenous Administration in Animals

Nieto

Alvar

Mullen³

et al. 2003

Antimicrob Agents Chemother

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“…However, because of the rapid blood clearance of these drugs (5,13,14,17), an increase in dose and dosing frequency has been recommended by the World Health Organization (18). The amount of exposure of the infectious parasite to pentavalent antimony is believed to be an important factor in eradicating the cutaneous leishmania disease.…”

mentioning

confidence: 99%

Skin uptake, distribution, and elimination of antimony following administration of sodium stibogluconate to patients with cutaneous leishmaniasis

Jaser

El-Yazigi

Kojan

et al. 1995

Antimicrob Agents Chemother

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We examined in this study the pharmacokinetics of Sb in the affected skin and normal skin of patients treated with sodium stibogluconate for cutaneous leishmaniasis and compared the results with those for the blood. The procedure was fully explained, and a written consent was obtained from each of nine patients. After a dose of sodium stibogluconate equivalent to 600 mg of Sb was administered intramuscularly, small skin biopsies were collected under local anesthesia at different time intervals from the circumferences of the lesions and simultaneously from normal skin. Antimony was measured in these biopsies after suitable ashing and processing by flameless atomic absorption spectrophotometry. The means (with standard errors of the means in parentheses) of the peak concentration, time to peak concentration, area under the curve, half-life, and mean residence time in lesions were 5.02 (1.43) g/g, 2.1 (0.4) h, 32.8 (6.1) g ⅐ h/g, 6.88 (0.54) h, and 10.4 (1.2) h, respectively, and those in normal skin were 6.56 (2.01) g/g, 2.6 (0.8) h, 44.0 (15.8) g ⅐ h/g, 5.44 (0.83) h, and 8.08 (1.34) h, respectively. There was no significant difference in any of these parameters between lesions and normal skin, whereas the differences in peak concentration, half-life, and mean residence time between lesions and whole blood were significant (P Յ 0.05). The penetration of Sb into skin, either affected or normal, as measured by the skin/blood area under the curve ratio appears to be complete, but the disposition is slow compared with that from the blood.The best treatment for leishmaniasis is currently achieved with pentavalent antimonials in the form of sodium stibogluconate (SSG) or meglumine antimonate. However, because of the rapid blood clearance of these drugs (5,13,14,17), an increase in dose and dosing frequency has been recommended by the World Health Organization (18). The amount of exposure of the infectious parasite to pentavalent antimony is believed to be an important factor in eradicating the cutaneous leishmania disease. Thus, delivering the dose by intralesion injections of SSG has recently been advocated (8,10,15). When the drug is administered intramuscularly, the contact with the parasite is undoubtedly controlled by the rate and extent at which this metal reaches and leaves the lesions following the administration of SSG. Therefore, knowledge of the kinetics of the uptake and disposition of this metal in affected skin is vital for optimization of the dosage regimens of these drugs in the treatment of cutaneous leishmaniasis. Although these drugs have been in use for more than four decades (11,16), no such study has yet been reported for SSG. Plasma kinetic data are clinically relevant to the extent that they reflect those of the site of action.We undertook to examine in this study the kinetics of Sb in the affected skin and normal skin of patients treated intramuscularly with sodium stibogluconate for cutaneous leishmaniasis and to compare the results with those for the blood samples of these patients. The impac...

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“…This recommended schedule was of 600 mg of Sb v per day during 10 days and at equal intervals another 10 days series could be added. Pentavalent antimony is rapidly excreted (Rees et al 1980, Sampaio et al 1980, Chulay et al 1988) resulting in sub-therapeutic blood levels in a few hours (Oster et al 1985) and so such rest periods are regarded as pharmacologically unsound. Chulay et al (1988) exposed the view point that treatment with pentavalent antimony depends on maintenance of a inhibitory drug concentration for most of the day.…”

Section: Discussionmentioning

confidence: 99%

High and low doses of antimony (Sb v) in American cutaneous leishmaniasis: a five years follow-up study of 15 patients

Mp¹,

Schubach²,

Araujo³

et al. 1996

Mem. Inst. Oswaldo Cruz

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Renal Clearance of Pentavalent Antimony (Sodium Stibogluconate)

Cited by 121 publications

References 4 publications

Pharmacokinetics, Toxicities, and Efficacies of Sodium Stibogluconate Formulations after Intravenous Administration in Animals

Pharmacokinetics, Toxicities, and Efficacies of Sodium Stibogluconate Formulations after Intravenous Administration in Animals

Skin uptake, distribution, and elimination of antimony following administration of sodium stibogluconate to patients with cutaneous leishmaniasis

High and low doses of antimony (Sb v) in American cutaneous leishmaniasis: a five years follow-up study of 15 patients

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