Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PYRIMETHAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2004

Drug monitoring of pyrimethamine during maintenance therapy of toxoplasmic encephalitis in patients with advanced HIV infection during HAART.

BACKGROUND: Prophylaxis of toxoplasmic encephalitis was performed with pyrimethamine in 6 patients with advanced HIV infection during combination therapy with protease inhibitors. MATERIAL/METHODS: Steady-state plasma pyrimethamine (PYR) levels were measured by gas chromatography. Protease inhibitor plasma concentrations were analyzed trough concentration by high pressure liquid chromatography. During a treatment period of 22I13 months a total of 93 samples from 6 patients were investigated, containing pyrimethamine and protease inhibitors. RESULTS: The mean pyrimethamine concentration was 1,108+/-459 ng/ml with a dosage of 37.5 mg/d and 1, 685+/-665 ng/ml with 50 mg/d. With the simultaneous use of indinavir (IDV), a mean pyrimethamine concentration of 2,165+/-273 ng/ml was found, significantly higher than in combination with saquinavir (SQV) and ritonavir (RTV) (1,192+/-178 ng/ml) or saquinavir and nelfinavir (NLV) (1,117+/-173 ng/ml). This effect was not considered clinically significant. Drug monitoring of protease inhibitors revealed a wide range of protease inhibitor levels. CONCLUSIONS: The statistically significant lower PYR concentrations with the SQV + RTV or SQV + NLV comedication in comparison to comedication with IDV were not considered clinically significant. Therapeutic drug monitoring of PYR and PI plasma levels can be recommended in patients during therapy with both PYR and PI, especially during therapy with a double PI regimen.

Adult↗
PubMed2005

Sulfadoxine-pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria: a randomized, multisite trial to guide national policy in Uganda.

The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.

Amodiaquine↗
PubMed1992

Pyrimethamine alone as maintenance therapy for central nervous system toxoplasmosis in 38 patients with AIDS.

We retrospectively assessed the efficacy of maintenance therapy with pyrimethamine alone in 38 patients with AIDS and central nervous system (CNS) toxoplasmosis. The diagnosis was based on clinical presentation and compatible CT scan abnormalities with subsequent response to therapy. Survival analysis was performed by the product limit method of Kaplan-Meier. Fourteen patients received maintenance therapy with 25 mg pyrimethamine per day (group 1), and 24 patients were treated with 50 mg per day (group 2). The median survival from initiation of maintenance therapy until death or end of the study for the entire study population was 32 weeks. Median survival in group 1 was 28 weeks, as compared with 36 weeks in group 2 (p = 0.34). Relapses occurred in 12 patients, six in group 1 and six in group 2. There was no significant difference in failure-free survival between the two treatment groups (p = 0.09). One patient in group 1 and two patients in group 2 experienced severe toxicity, requiring discontinuation of therapy. All three patients relapsed and died. Two patients in group 2 who stopped treatment on their own initiative also had relapses. Thus, all five patients who discontinued therapy had relapses. Five of 13 patients in group 1 and two of 20 patients in group 2 relapsed during continuous therapy with pyrimethamine (p = 0.13); these seven patients responded to reintroduction of combination therapy (n = 6) or treatment with 50 mg pyrimethamine per day (n = 1). The results of our retrospective analysis suggest that maintenance therapy with oral pyrimethamine, 50 mg per day, in AIDS patients with CNS toxoplasmosis is effective.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Experimental study of the action of antimalarial agents with respect to therapy in porphyria. Combined effect of chloroquine and pyrimethamine].

On an experimental model created from semiaerobically cultivated yeast cells of Caccharomyces cerevisiae (RIMB-75) the authors tested the effect of antimalarics used or tested for treatment of symptomatic liver porphyria. Chloroquine and pyrimethamine inhibited the synthesis of porphyrins, whereby pyrimethamine was more effective. Chloroquine released moreover intracellular porphyrins, contrary to pyrimethamine, which caused their intracellular cumulation. An equimolar combination of the two preparations preserved the inhibitory action of pyrimethamine, and the intracellular porphyrin content was reduced. Based on experimental results the suggested combination of chloroquine and pyrimethamine was successfully tested in clinical work.

Chloroquine↗
PubMed1985

An open, randomized, phase III clinical trial of mefloquine and of quinine plus sulfadoxine-pyrimethamine in the treatment of symptomatic falciparum malaria in Brazil.

The clinical and parasitological response of adult male patients to mefloquine and to a combination of quinine and sulfadoxine-pyrimethamine during the treatment of falciparum malaria was compared. These patients were from an area in Brazil where Plasmodium falciparum is showing increasing resistance to quinine and to sulfadoxine-pyrimethamine. The drugs were administered to 100 patients (50 in each group), based on a randomized study design.The rates of clearance of parasitaemia and fever were similar in both groups. However, the parasitological cure rate ("S" response) was 100% for mefloquine but only 92% for quinine plus sulfadoxine-pyrimethamine. Tolerance was good in both groups. The main side-effects (nausea, vomiting, abdominal pain, and dizziness) were mild, transient and required no specific treatment. Nausea and vomiting were more frequent in patients who received quinine plus sulfadoxine-pyrimethamine, while abdominal pain and loose stools or mild diarrhoea were more frequent in the mefloquine group. Tinnitus and hearing difficulty were observed following the administration of quinine plus sulfadoxine-pyrimethamine, but not after mefloquine treatment. Laboratory tests of various haematological and biochemical parameters were not adversely affected in either group after drug administration.It can be concluded that mefloquine, given in a single oral dose of 1000 mg, is highly effective, well tolerated, and safe for the treatment of falciparum malaria in adult males in Brazil.

Adolescent↗
PubMed1985

A phase I clinical trial of Fansimef (mefloquine plus sulfadoxine-pyrimethamine) in Brazilian male subjects.

A double-blind, randomized phase I clinical trial was carried out to compare Fansimef (a fixed-dose combination of mefloquine, sulfadoxine, and pyrimethamine) with sulfadoxine and pyrimethamine (Fansidar) for safety and tolerance. Twenty adult male Brazilian subjects from malaria endemic areas were studied for a period of 66 days, which included 2 days before and 63 days after drug administration.Both drugs were well tolerated and safe, as seen from the absence of drug-induced changes in the various laboratory, haematological, and biochemical parameters measured. Fansimef produced a complete clearance of parasites on day 3, with an "S" type response in one subject who had blood smears which were positive for Plasmodium falciparum on day 0. Two subjects in the sufladoxine-pyrimethamine group also had P. falciparum infections on day 0; the parasitaemia was cleared on day 2 in one of these subjects and on day 3 in the other, but an early RI response (recrudescence) was observed in the former case. Relapses due to P. vivax occurred in both groups.Side-effects due to Fansimef included mild dizziness, nausea, and vomiting. The incidence of dizziness and nausea was similar in the sulfadoxine-pyrimethamine group. In both groups, these side-effects were mild, short-lived and did not require specific treatment. Thus, Fansimef in an oral dose of three tablets (total of 750 mg mefloquine (base) plus 1500 mg sulfadoxine plus 75 mg pyrimethamine) was found to be well tolerated and safe.

Adult↗
PubMed1997

[Azithromycin combined with pyrimethamine in the treatment of neurotoxoplasmosis, in an AIDS patient].

We report one case of successful treatment of cerebral toxoplasmosis in acquired immunodeficiency syndrome (AIDS) with azithromycin combined with pyrimethamine. Toxoplasmic encephalitis had been diagnosed on the basis of multiple lesions exhibiting ring like contrast enhancement on double contrast Computed Tomographic (CT) scan of the brain. Thereby our patient had been treated with pyrimethamine 25 mg/die, after an attack dose of 100 mg in the first day, and clindamycin 2400 mg/die, because of sulfa-drug allergy, but clindamycin had to be discontinued because of rash development. At this point azithromycin, at a dose of 1000 mg/die for 21 days and 1500 mg a week for the following 50 days of follow-up, was added to pyrimethamine. Follow-up CT scan after 20 days of treatment (10 with clindamycin+pyrimethamine and 10 with azithromycin+pyrimethamine) revealed partial resolution of the brain lesions and subsequently (after 50 and 80 days of treatment) complete resolution.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Mass spectrometry in the verification of pyrimethamine poisoning].

A 17 years old male patient with Pyrimethamin therapy was released from our department by emphasising the necessity of continuous control. A month later the patient was accepted again with serious anaemia. Since the patient did not follow the instructions Pyrimethamin intoxication was presumed, but it had to be proved. At last the drug in the plasma was identified and quantified by mass spectrometry. The plasma concentration of Pyrimethamin was five times higher than the therapeutic level. The rapid analysis (4 hours after taking of blood) and adequate treatment resulted in rapid improvement with the concomitant decrease of plasma Pyrimethamin concentration. During clinical treatment the level of Pyrimethamin in the plasma was followed by mass spectrometry.

Adolescent↗
PubMed1998

Nifurtimox plus pyrimethamine for treatment of murine toxoplasmosis.

In the search for novel antitoxoplasmic agents, we evaluated the efficacy of nifurtimox (3-methyl-4[5'-nitrofurfurylidene-amino]-tetrahydroe-4H-1,4- thiazine-1,1-dioxide), an antiprotozoal drug effective against trypanosomiasis, in an experimental model of acute toxoplasmosis in mice. One hundred NIH mice were inoculated intraperitoneally, each with 2,614 RH tachyzoites of Toxoplasma gondii, and randomly allocated into 5 groups (n = 19-21). Animals from each group were orally treated for 10 days either with nifurtimox 25 mg/kg/day (NF1), nifurtimox 50 mg/kg/day (NF2), pyrimethamine 60 mg/kg/day (P), the combination nifurtimox 50 mg/kg/day plus pyrimethamine 60 mg/kg/day (NF2-P), or with corn oil (controls). Survival of mice was recorded daily for 1 mo after the experimental infection. Comparisons of cumulative mortality between groups were made applying the chi2 test. Mean survival time was longer in animals from P and NF2-P groups than those from NF1, NF2, and control groups. Cumulative mortality was less in mice from the NF2-P group (25%), than that in mice from the P (65%), the NF1 (100%), the NF2 (89%), or the control (95%) groups (P < 0.01). The doses of nifurtimox used in the present study were not significantly effective against murine toxoplasmosis. However, when combined with pyrimethamine, a strong anti-toxoplasma effect was obtained in comparison with survival rates associated with pyrimethamine or nifurtimox alone. It seems feasible that nifurtimox inhibits the replication of T. gondii tachyzoites similar to that of other protozoans, e.g., Trypanosoma and Leishmania. It will be important to determine if the reduction of mortality in mice treated with the nifurtimox-pyrimethamine combination results from summation or from synergism. Further studies on the toxic mechanisms exerted by nifurtimox on T. gondii seem warranted.

Administration, Oral↗
PubMed1998

Effect of intramuscular sulfadoxine-pyrimethamine on pregnant Wistar rats.

BACKGROUND: Sulfadoxine-pyrimethamine preparations are used commonly for the treatment and or prevention of malaria in the endemic regions of Sub-Sahara Africa. Pyrimethamine alone has been shown to be teratogenic in rats, mice and hamsters, and others animals. METHODS: Pregnant Wistar rats were divided into three groups. The first group received a therapeutic dose of sulfadoxine-pyrimethamine (0.72 mg/kg body weight) intramuscularly (1.m) on the 5th, 12th, and 19th of gestation (3 doses). The second group received a similar dose on the 10th and 17th days of gestation (2 doses); the third group received the same dose on the 15th and 22nd days of gestation (2 doses). Controls for each group received 2 ml of physiological saline through the same route on similar days instead of the drugs. RESULTS: All control animals produced normal litters (average 5.6), but group 3a animals produced litters with no obvious congenital malformations (average 4.8). Animals in groups 1a and 2a produced no litters. When they were sacrificed, they showed implantation sites in their uterine horns. Histological sections of these implantation sites showed that the embryos had been resorbed. CONCLUSIONS: Therapeutic dose of sulfadoxine-pyrimethamine (0.72 mg/kg body weight) administered early in gestation resulted in complete embryo resorption in Wistar rats. The use of these preparations in early pregnancy in man demands caution.

Animals↗
PubMed2002

Inhibitory effects of ascorbic acid and folinic acid on chromosome aberrations induced by pyrimethamine in vitro.

In this study, the anticlastogenic effects of ascorbic acid and the protective effect of folinic acid against the formation of chromosomal aberrations in humans by pyrimethamine were investigated. Pyrimethamine is a folic acid antagonist used for the treatment of malaria and toxoplasmosis. In this study, 18 different healthy people, who do not drink alcohol and are non-smokers, were chosen as an experimental group; 0.025 mg/ml pyrimethamine was given to the lymphocyte culture, which had been prepared with the peripheral blood taken from this group. After that each of the following doses were given to the same culture: 20, 40, and 80 mM of ascorbic acid and 25, 50, and 100 mM of folinic acid. The results of the cytogenetic evaluation showed that the aberrations due to pyrimethamine in the chromosomes were reduced by ascorbic acid and folinic acid significantly, depending on the given dose.

Ascorbic Acid↗
PubMed1991

The clastogenic effect of pyrimethamine (Daraprim) on human chromosomes in lymphocyte cultures.

In this study the clastogenic effect of pyrimethamine (Daraprim), a folic acid antagonist used for the treatment of toxoplasmosis and malaria on human chromosomes, was investigated. Pyrimethamine was added to in vitro lymphocyte cultures at six different concentrations: 0.05 (normal therapeutic dose), 0.1, 0.2, 0.4, 0.8, and 1.6 mg/ml. No proliferation was observed in any of the cultures containing 1.6 mg/ml pyrimethamine. The results of the cytogenetic evaluations show that the frequency of breaks and gaps increase significantly in dose-dependent manner. Thus, pyrimethamine has a clastogenic effect on human chromosomes.

Adolescent↗
PubMed1992

Efficacy of pyrimethamine for the prevention of donor-acquired Toxoplasma gondii infection in heart and heart-lung transplant patients.

Seven (11%) of the first 65 patients who received heart transplants at Papworth Hospital were mismatched for Toxoplasma gondii. Of these, four (57%) experienced T. gondii infection and two died. The remaining two had severe symptoms and received anti-T-gondii chemotherapy for a year after transplantation. In an attempt to reduce the impact of donor-acquired T. gondii in our heart transplant recipients, we decided in April 1984 to give prophylactic pyrimethamine to all T. gondii-mismatched patients. In this study, 7 years later, we review the efficacy of this policy. Five of 37 (14%) patients given prophylactic pyrimethamine acquired T. gondii infection; only one was symptomatic, and none died. This compares with 100% symptomatic infection in the pre-1984 patients, who did not receive prophylactic pyrimethamine. We believe that our experience has shown that pyrimethamine is effective in reducing the incidence and severity of primary donor-acquired T. gondii infection in mismatched heart and heart-lung transplant recipients.

Adolescent↗
PubMed1991

A retrospective study of primary and maintenance therapy of toxoplasmic encephalitis with oral clindamycin and pyrimethamine.

Fourteen patients with AIDS and toxoplasmic encephalitis, who could not be treated with the standard regimen of pyrimethamine and a sulfonamide due to a previous history of bone marrow suppression and severe allergic reactions to sulfonamides, were treated with oral clindamycin and pyrimethamine. All 14 patients received a 100 mg loading dose of pyrimethamine orally followed by 50 mg/day plus clindamycin orally (600-900 mg q8h). The duration of primary treatment ranged from 6 to 8 weeks. All patients also received folinic acid (15 mg/day orally). Maintenance therapy consisted of 25 mg/day of pyrimethamine and clindamycin (300 mg q6h or 450 mg q8h). A complete or partial clinical or neuroradiological response was observed in all patients at the end of two months of primary therapy. Ten of 14 patients showed complete resolution of clinical signs, and 8 of 14 patients showed complete resolution of neuroradiologic signs. All 14 patients continued the maintenance regimen, and although there were no relapses, symptoms that had not resolved by the end of the second month of acute therapy tended to remain unchanged.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine.

The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or IgA-antibodies on 3 mm blood spots collected from phenylketonuria [PKU cards (Guthrie cards)]. Toxoplasma-infected children received 3 months' continuous treatment with 50-100 mg/kg per day sulfadiazine in two separate administrations and 1 mg/kg per day pyrimethamine after a 1-day loading dose of 2 mg/kg, and folinic acid 7.5 mg was administered twice weekly. Blood cell counts and body weight were recorded during follow-up. The plasma concentrations of pyrimethamine and sulfadiazine were analysed in a subgroup of seven children, using high performance liquid chromatography with ultraviolet and mass spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5x10(9)/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was <or=0.5x10(9)/l or lower in 4/29 (13.8%). None of the children had anaemia or thrombocytopenia. The drugs did not affect weight gain. Mean plasma drug concentrations varied between 1.3 microg/ml and 2.2 microg/ml for pyrimethamine and between 60 microg/ml and 86 microg/ml for sulfadiazine. Treatment efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits.

Antiprotozoal Agents↗
PubMed2000

Thrice-weekly sulfadiazine-pyrimethamine for maintenance therapy of toxoplasmic encephalitis in HIV-infected patients. Spanish Toxoplasmosis Study Group.

An open, randomised, multicentre trial was conducted to evaluate the efficacy of thrice-weekly versus daily therapy with sulfadiazine-pyrimethamine in the prevention of relapses of toxoplasmic encephalitis in HIV-infected patients. Between February 1994 and July 1997, 124 patients with HIV infection were enrolled after resolution of the first acute episode of toxoplasmic encephalitis treated with sulfadiazine-pyrimethamine. Patients were randomly assigned to receive either a daily regimen consisting of sulfadiazine (1 g) twice a day plus 25 mg pyrimethamine and 15 mg folinic acid daily (n = 58), or a thrice-weekly regimen consisting of the same doses of sulfadiazine and folinic acid plus 50 mg pyrimethamine (n = 66). After a median follow-up period of 11 months (range 1-39 months), no differences were found in the incidence of toxoplasmic encephalitis relapses between the groups, there being 14.9 episodes per 100 patient-years (95% CI: 2.8-20.2) in the daily-regimen group versus 14.1 episodes (95% CI: 2.3-17.2) in the intermittent-regimen group. The estimated cumulative percentages of relapse at 12 months were 17% and 19%, respectively (P = 0.91). In a Cox multivariate analysis, not taking antiretroviral therapy was the only variable independently associated with relapse (adjusted risk ratio: 4.08; 95%CI: 1.32-12.66). Baseline CD4+ cell counts, prior AIDS, mental status, sequelae and allocated maintenance therapy regimen were not independent predictors of relapse. No differences were observed in the survival rate (P = 0.42), or in the incidence of severe adverse effects (P = 0.79). The efficacy of the thrice-weekly regimen was similar to that of the daily regimen in the prevention of relapses of toxoplasmic encephalitis. Administration of antiretroviral therapy was the only factor associated with a lower incidence of relapse.

AIDS-Related Opportunistic Infections↗
PubMed1988

Double-blind dose finding study of mefloquine-sulfadoxine-pyrimethamine in children with acute falciparum malaria.

Three different doses of a combination of mefloquine-sulfadoxine-pyrimethamine (MSP), given double-blind as a single dose to 60 children, were evaluated for efficacy and tolerance. The children, 42 boys and 18 girls aged between 5 and 15 years, received a mefloquine dose equivalent to 1, 1.5, or 2 standard MSP (Fansimef) tablets. Radical cure was obtained in all patients with only mild to moderate side effects of nausea and vomiting, which were not worse in the higher dose groups. For children living in an endemic malarious area, a single dose of mefloquine 7.1-12.5 mg/kg, given in combination with sulfadoxine (14.3-25.0 mg/kg) and pyrimethamine (0.7-1.3 mg/kg), is a safe and effective treatment for uncomplicated chloroquine-resistant Plasmodium falciparum malaria. This dose of MSP is approximately 10 mg/kg, 20 mg/kg and 1.0 mg/kg respectively of mefloquine, sulfadoxine and pyrimethamine, which is equivalent to a single standard tablet of Fansimef (mefloquine, 250 mg; sulfadoxine, 500 mg; pyrimethamine, 25 mg) given to a child weighing 20-30 kg.

Adolescent↗
PubMedDate not supplied

Sensitivity of Plasmodium falciparum in vivo to chloroquine and pyrimethamine-sulfadoxine in Rwandan patients in a refugee camp in Zaire.

Resistance of Plasmodium falciparum to available antimalarial drugs is now thought to be spreading progressively throughout sub-Sahara Africa. In this study we measured the susceptibility of P. falciparum to chloroquine and pyrimethamine-sulfadoxine in vivo in Rwandan patients living in Kibumba refugee camp in Goma, Zaire. Of the 39 cases treated with chloroquine, only 8 (20.5%) showed sensitive or RI (delayed) response and 31 (79.5%) demonstrated resistance at RI (30.8%), RII (33.3%( and RIII (15.4%) levels. Of the 38 individuals receiving pyrimethamine-sulfadoxine, 13 (34.2%) showed sensitive or RI (delayed) responses, and 25 (65.%) showed resistance at RI (26.3%), RII (36.8%) and RIII (2.6%) levels. Both chloroquine and pyrimethamine-sulfadoxine reduced parasite counts by at least 75% in the majority of the patients within 2 d of treatment. A greater proportion of children with malnutrition showed a higher mean geometric parasite density and slower parasite clearance in vivo than those without malnutrition. Moreover, the frequency and degree of resistance were more pronounced in children with malnutrition. Moreover, the frequency and degree of resistance were more pronounced in children with malnutrition. The results suggest the existence of resistance to chloroquine and pyrimethamine-sulfadoxine. However, the drugs are still effective in significantly reducing parasitaemia and they can still be used as drugs of first and second choice in the region, even in the face of some degree of resistance.

Adolescent↗