The Hematologic Toxicity of Pyrimethamine (Daraprim) in Man

Kaufman, Herbert E.; Geisler, Philip H.

doi:10.1001/archopht.1960.01840010142016

Cited by 40 publications

(9 citation statements)

References 14 publications

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“…Hematologic reactions such as megaloblastic anemia and bone marrow suppression are dose related. A report of daily dosing of PYR (25 to 100 mg/day) with sulfa drugs (either sulfadiazine, sulfamethazine, or sulfamerazine) in 87 cases of toxoplasma uveitis demonstrated a dose-related bone marrow suppression that completely reversed with folic acid supplementation or cessation of the drug (28,68). Since this occurred after 7 to 10 days of daily dosing, it is not expected that a second conventional dose of SP would result in bone marrow suppression, particularly in the context of conventional prepartum folic acid supplementation.…”

Section: Figmentioning

confidence: 99%

Optimal Antimalarial Dose Regimens for Sulfadoxine-Pyrimethamine with or without Azithromycin in Pregnancy Based on Population Pharmacokinetic Modeling

Salman

Baiwog

Page‐Sharp

et al. 2017

Antimicrob Agents Chemother

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Optimal dosing of sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment in pregnancy remains to be established, particularly when coadministered with azithromycin (AZI). To further characterize SP pharmacokinetics in pregnancy, plasma concentration-time data from 45 nonpregnant and 45 pregnant women treated with SP-AZI (n ϭ 15 in each group) and SP-chloroquine (n ϭ 30 in each group) were analyzed. Population nonlinear mixed-effect pharmacokinetic models were developed for pyrimethamine (PYR), sulfadoxine (SDOX), and N-acetylsulfadoxine (the SDOX metabolite NASDOX), and potential covariates were included. Pregnancy increased the relative clearance (CL/F) of PYR, SDOX, and NASDOX by 48, 29, and 70%, respectively, as well as the relative volumes of distribution (V/F) of PYR (46 and 99%) and NASDOX (46%). Coadministration of AZI resulted in a greater increase in PYR CL/F (80%) and also increased NASDOX V/F by 76%. Apparent differences between these results and those of published studies of SP disposition may reflect key differences in study design, including the use of an early postpartum follow-up study rather than a nonpregnant comparator group. Simulations based on the final population model demonstrated that, compared to conventional single-dose SP in nonpregnant women, two such doses given 24 h apart should ensure that pregnant women have similar drug exposure, while three daily SP doses may be required if SP is given with AZI. The results of past and ongoing trials using recommended adult SP doses with or without AZI in pregnant women may need to be interpreted in light of these findings and consideration given to using increased doses in future trials.

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Section: Figmentioning

confidence: 99%

Optimal Antimalarial Dose Regimens for Sulfadoxine-Pyrimethamine with or without Azithromycin in Pregnancy Based on Population Pharmacokinetic Modeling

Salman

Baiwog

Page‐Sharp

et al. 2017

Antimicrob Agents Chemother

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show abstract

“…Current therapy with the combination of pyrimethamine and sulphadiazine (or triple sulphonamides) (Eyles & Coleman, 1955) has the disadvantage of producing many adverse and even toxic effects (Kutscher, Lane & Segael, 1954;Kaufman & Geisler, 1960). In some cases, especially in AIDS patients, these effects force discontinuation of therapy, leading to an almost inevitable relapse which frequently will not respond to the same therapy again (Haverkos, 1987;Wanke et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Activity of spiramycin against Toxoplasma gondii in vitro, in experimental infections and in human infection

Chang

Péchère

1988

Journal of Antimicrobial Chemotherapy

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“…However, the mortality rate among immunodeficient patients with toxoplasma encephalitis treated with this combination approaches 70% (Levy, Bredesen & Rosemblum, 1985), and the toxicity of the combination precludes its use during pregnancy (Kutscher, Lane & Segael, 1954;Kaufman & Geisler, 1960). Therefore, there is a need for alternative therapy for this disease.…”

Section: Introductionmentioning

confidence: 99%

Activity of roxithromycin against Toxoplasma gondii in murine models

Chang

Péchère

1987

Journal of Antimicrobial Chemotherapy

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Investigations into the activity of roxithromycin against murine toxoplasma infections are reviewed. Roxithromycin is an active drug against murine toxoplasmosis after intraperitoneal challenge with the RH strain of Toxoplasma gondii. Roxithromycin protected 100% of mice after five daily doses of 540 mg per kg administered by gavage. The cure rate after treatment of peritoneal infections seemed to be related to the length of the therapy. Roxithromycin also decreased the number of toxoplasma cysts, after intracerebral infection with the C56 strain and showed synergistic activity when combined with gamma interferon. Thus, roxithromycin could be a worthwhile alternative to current therapy against toxoplasma infections. Clinical studies on its activity and safety, especially in pregnancy, are warranted.

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The Hematologic Toxicity of Pyrimethamine (Daraprim) in Man

Cited by 40 publications

References 14 publications

Optimal Antimalarial Dose Regimens for Sulfadoxine-Pyrimethamine with or without Azithromycin in Pregnancy Based on Population Pharmacokinetic Modeling

Optimal Antimalarial Dose Regimens for Sulfadoxine-Pyrimethamine with or without Azithromycin in Pregnancy Based on Population Pharmacokinetic Modeling

Activity of spiramycin against Toxoplasma gondii in vitro, in experimental infections and in human infection

Activity of roxithromycin against Toxoplasma gondii in murine models

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