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PubMed1987

Comparison of different methods for determining pyrimethamine susceptibility in P. falciparum malaria.

Resistance against pyrimethamine was determined for Plasmodium falciparum adapted to continuous culture and for 'wild' isolates. The IC50 values were found by incubating for 48 hours or 48 + 24 hours (the last 24 hours without drug) and counting either the total parasites or the ring forms only. It was found that in continuous, asynchronous cultures the IC50 values were not significantly influenced by the choice of method. The IC50 value found when counting ring forms only were slightly lower than those obtained by counting the total number of parasites, but the confidence limits did overlap. The same was the case for the 48 hours and 48 + 24 hours tests. The isolates collected directly from patients with acute malaria were incubated for 48 hours. The percentage of ring forms in the control wells varied between 21% and 63% after 48 hours, indicating that the plasmodial cycle could be prolonged under test conditions. The IC50 values were estimated in two ways, by counting either the total parasitaemia or the ring forms only. On theoretical grounds, estimating the IC50 value from the number of ring forms is the most satisfactory method, as this number corresponds to the number of undamaged schizonts. The IC50 values found by 3H-hypoxanthine incorporation were lower than those found by any other method.

Animals↗
PubMed1988

Sensitivity of Plasmodium falciparum to mefloquine-sulphadoxine-pyrimethamine (Fansimef) in vivo and to mefloquine alone in vitro in Nigeria.

In Nigeria chloroquine remains the drug of choice for the treatment of falciparum malaria, since chloroquine resistance is not yet a problem. Nevertheless, in view of the rapid spread of multi-resistant Plasmodium falciparum in Africa it is desirable to test alternative drugs for efficacy and safety. To this end, we undertook a comparative controlled trial of the new triple combination, mefloquine-sulphadoxine-pyrimethamine (MSP, Fansimef) with chloroquine in a group of Nigerian children with symptomatic falciparum malaria. Our results showed that Fansimef was an effective blood schizontocide against the Nigerian strain of P. falciparum and was well tolerated. In particular, sinus bradycardia, which was frequently observed with Fanismef in the trials conducted in Zambia, was not seen in any of the Nigerian patients. In vitro sensitivity tests done on 26 P. falciparum isolates showed that all isolates were susceptible to complete inhibition by mefloquine, but the minimum concentration which produced complete inhibition in some isolates was higher than expected for fully sensitive parasites.

Animals↗
PubMed1996

The effect of oral iron therapy during treatment for Plasmodium falciparum malaria with sulphadoxine-pyrimethamine on Malawian children under 5 years of age.

In sub-Saharan countries, although malaria and malaria-associated anaemia are major public health problems, the usefulness of supplementary iron treatment for children with malaria-associated anaemia is unknown. In a 6-week period during the 1995 rainy season, 222 Malawian children aged < 5 years, who sought treatment for malaria, had > or = 500 parasites/microliter blood and at least 5 g haemoglobin (HB)/dl blood and whose parents gave consent, were randomized into a prospective study comparing the efficacy of sulphadoxine- pyrimethamine only (SP), SP plus daily iron (SPD) and SP plus weekly iron (SPW) as treatment for malaria-associated anaemia. The patients had their HB concentrations measured on enrollment (day 0), just before antimalarial treatment, and on days 3, 7, 14, 21 and 28; 215 (96.8%) completed the 28-day study. Among the children with 5-8 g HB/dl on enrolment, HB gain by the end of the study was significantly greater than in the children with > 8 g HB/dl initially (4.1 v. 2.2 g/dl; P < 0.05), and those in the SPD group gained significantly more HB by days 21 and 28 (3.6 and 4.9 g/dl, respectively) than those in either the SPW (2.7 and 3.7 g/dl, respectively) or the S2 groups (2.6 and 3.5 g/dl, respectively); there was no difference in HB gain between the SP and SPW groups. Type of treatment had no apparent effect, at any time during the study, on HB gains in those patients who had > 8 g HB/dl on enrolment. Thus the children with 5-8 g HB/dl on enrolment benefited from daily iron therapy whereas those with > 8 g HB/dl derived no significant benefit; improvement in HB depended most on whether enrolment HB was < or = 8.0 g/dl. As treatment with an effective antimalarial drug resulted in HB gains, irrespective of treatment group or HB concentration at enrolment, the anaemia observed may be mostly related to malaria. However, as a larger proportion of the iron-treated patients failed to clear their parasitaemias than of those given SP alone, oral iron may inhibit SP action. It is therefore recommended that, for children with both malaria and malaria-associated anaemia, the malaria should first be cleared with an effective antimalarial drug, such as SP, before the anaemia, if it still persists, is treated with iron.

Antimalarials↗
PubMed1997

Parasitological and haematological responses to treatment of Plasmodium falciparum malaria with sulphadoxine-pyrimethamine in southern Malawi.

In 1993, Malawi introduced sulphadoxine-pyrimethamine (SP) for the treatment of uncomplicated, Plasmodium falciparum malaria and became the first country in Africa to abandon chloroquine for first-time therapy. This decision produced an urgent need to monitor local P. falciparum for resistance to SP and to establish both clinical and parasitological criteria for drug failure. The parasitological and haematological responses to treatment of malaria in southern Malawi with SP have now been investigated. Children, aged 6-59 months, who attended health-care facilities with uncomplicated infections of P. falciparum alone were enrolled in the study. Each received standard treatment with SP and paracetamol and was followed-up on days 3, 7, 14, 21 and 28 post-treatment. Haemoglobin (Hb) was measured on days 0, 14 and 28. Zinc erythroprotoporphyrin (ZP) was estimated once during follow-up, as an indicator of iron status. Of 107 children enrolled, 84 children (78.5%) were followed for 14 days or until clinical failure. The parasitological success rate amongst the latter was 90.5% (76/84). One child showed poor parasite clearance (with a parasitaemia at day 3 > 25% of that at day 0), one had a low level of persistent parasitemia, and six were parasitaemic on day 14 after being parasite free on day 7. A 14-day follow-up increased the detection of parasitological failure by 7.2%. Haematological recovery on day 14 was not significantly different for parasitological successes or failures. The geometric mean parasite density (GMPD) was significantly lower in children classified as iron deficient (ZP > or = 3.0 micrograms/g Hb) and these children were significantly more likely to be severely anaemic (Hb < 8 g/dl) at day 0. Parasitological responses and haemoglobin levels 28 days after SP treatment were independent of ZP levels. These results show that, 2 years after the introduction of SP in Malawi for the treatment of uncomplicated, P. falciparum malaria, the drug combination remains effective in 90.5% of cases. Iron status did not affect parasitological recovery. Although iron-deficient children were at greater risk of severe anaemia they did not show significantly reduced recovery from malarial anaemia.

Anemia↗
PubMed1998

Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine as a treatment for uncomplicated malaria--a systematic review.

The 4-aminoquinolines, chloroquine or amodiaquine, have long been the drugs of choice for treating uncomplicated, falciparum malaria in Africa, although resistance to them is now common. Sulfadoxine-pyrimethamine (SP) is the usual alternative when 4-aminoquinoline treatment fails. A combination-treatment regimen could combine the rapid symptom relief offered by the 4-aminoquinolines with the prolonged parasiticidal activity of SP, and also slow down development of resistance to the individual drugs. A systematic review of randomized trials was conducted so that the evidence of effectiveness and safety of such combination treatment could be summarized and compared with the results of treatment with either drug given alone. The results of trials were sought by searching through electronic databases and by contact with researchers in the field. Five studies were identified. Although there are few data, there is evidence that control of clinical symptoms is better when a 4-aminoquinoline is used with SP than when SP is used alone, and the cure rate also tends to be higher with the combination regimen. No evidence of serious side-effects was found. Larger scale trials are needed if this combination is to be adopted more widely.

Amodiaquine↗
PubMed1998

An evaluation of the effects of intermittent sulfadoxine-pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi.

The prevalence of infection with malarial parasites and the incidence of anaemia and delivery of infants with low birthweight (LBW) were investigated in 575 Malawian mothers who received one, two or three doses of sulfadoxine-pyrimethamine (SP) during pregnancy. All the subjects were enrolled at their first antenatal visit and all delivered at hospital. The prevalence of Plasmodium falciparum infection at first antenatal visit was 35.3% in primigravidae and 13.6% in multigravidae (P < 0.001). Mean haemoglobin concentration was significantly lower in primigravidae than in multigravidae (8.8 v. 9.5 g/dl; P < 0.001). Of the 233 women tested for HIV infection, 18.8% of the primigravidae and 23.7% of the multigravidae were seropositive. At delivery, there was no significant difference in parasite prevalence in peripheral or placental blood between women who had received one or two antenatal doses of SP. The multigravidae who had received two doses of SP had higher mean haemoglobin concentrations than those who had received just one (P = 0.009) [this difference was not seen in the primigravidae (P = 0.92)]. However, linear regression analysis indicated that the haematinic supplements given to the subjects contributed more to this increase in haemoglobin concentration than the SP. The mean birthweights were higher, and incidence of LBW lower in babies born to primi-and multi-gravidae who had received two or three doses of SP treatment than those seen in babies born to women who had had just one dose (P < 0.03 for each). The odds ratio for LBW in primigravidae compared with multigravidae decreased from 3.2 to 1.0 as the number of SP doses increased from one to three. The benefit of three doses (compared with none) was equivalent to the population-attributable risk of LBW in primigravidae being reduced from 34.6% to 0%. Subjects who were seropositive for HIV were twice as likely to give birth to LBW babies as the other subjects. The use of SP was not associated with maternal side-effects or perinatal complications. The present results indicate that multiple doses of SP taken during pregnancy will lead to a highly significant reduction in the incidence of LBW in infants born to primigravidae, even if the women have HIV infections. This reduction is observable even when parasite prevalence at delivery is high because of re-infections in late pregnancy; reduction in parasite prevalence earlier in pregnancy, as the result of SP treatment, leads to improved foetal growth.

Adolescent↗
PubMed1993

Doxycycline and pyrimethamine for toxoplasmic encephalitis.

Clinical improvement is reported in a 40-year-old man with AIDS and presumed toxoplasmic encephalitis, who was treated with doxycycline, 400 mg, and pyrimethamine, 25 mg, daily. Computerised tomography (CT) scanning of the brain showed complete resolution of 2 ring-enhanced lesions within 5 weeks.

AIDS-Related Opportunistic Infections↗
PubMed1996

A comparative study of parenteral chloroquine, quinine and pyrimethamine-sulfadoxine in the treatment of Gambian children with complicated, non-cerebral malaria.

Ninety-two children with complicated, but not cerebral, Plasmodium falciparum malaria, aged 1-9 years, were recruited between August 1992 and December 1994 to an open, randomized trial of parenteral chloroquine (28), pyrimethamine-sulfadoxine (P-S) (36) and quinine (28). The median fever clearance time was shorter for chloroquine (27 hours) than for quinine (42 hours) or for P-S (36 hours) (P = 0.02 and P = 0.06, respectively). The parasite clearance times were similar for chloroquine and P-S, but significantly shorter for chloroquine compared with quinine (54 hours vs 66 hours) (P = 0.007) and for P-S compared with quinine (42 hours vs 66 hours) (P < 0.001). However, three children who received chloroquine and three who received P-S required a change to treatment with quinine because of a clinical failure of their initial treatment. Four children died, one in the chloroquine group, one in the quinine group and two in the P-S group. Despite a high level of chloroquine resistance in the community, the majority of Gambian children with complicated malaria responded satisfactorily to parenteral chloroquine given under supervision. The clinical failure rates of chloroquine and P-S were similar. Parenteral chloroquine and P-S remain adequate treatments for complicated, non-cerebral malaria in Gambian children, provided children can be kept under close clinical observation so as to detect early any treatment failures. Parenteral P-S has the advantage that only one dose is required.

Antimalarials↗
PubMed2003

Treatment history and treatment dose are important determinants of sulfadoxine-pyrimethamine efficacy in children with uncomplicated malaria in Western Kenya.

This study retrospectively studied amendable determinants of sulfadoxine-pyrimethamine (SP) efficacy involving 2869 treatments among 1072 Kenyan children <5 years old who had uncomplicated malaria. The dose was based on age: one-quarter tablet was given to infants <1 year old, one-half tablet was given to 1-3-year-old children, and a full tablet was given to 4-year-old children. Only 23.5% received the internationally recommended target dose of 25/1.25 mg of SP per kg of body weight. SP intake in the previous 15-35 days (adjusted relative risk, 1.67; 95% confidence interval, 1.35-2.07) and low SP dose (<27.5/1.375 mg/kg) (adjusted relative risk, 1.58; 95% confidence interval, 1.17-2.13) explained 38% of parasitological treatment failures by day 7. Patients with recent SP intake are likely to have recrudescent infections and may need close follow-up if treated with SP or alternative treatment. Applying our weight-for-age data to 31 existing age-based SP dose recommendations predicted that 22 of them would result in underdosing of >25% of children <5 years. Many age-based dose recommendations need urgent revision, because SP is increasingly used as first-line treatment in sub-Saharan Africa.

Age Factors↗
PubMed2003

Randomized, controlled trial of daily iron supplementation and intermittent sulfadoxine-pyrimethamine for the treatment of mild childhood anemia in western Kenya.

A randomized, placebo-controlled treatment trial was conducted among 546 anemic (hemoglobin concentration, 7-11 g/dL) children aged 2-36 months in an area with intense malaria transmission in western Kenya. All children used bednets and received a single dose of sulfadoxine-pyrimethamine (SP) on enrollment, followed by either intermittent preventive treatment (IPT) with SP at 4 and 8 weeks and daily iron for 12 weeks, daily iron and IPT with SP placebo, IPT and daily iron placebo, or daily iron placebo and IPT with SP placebo (double placebo). The mean hemoglobin concentration at 12 weeks, compared with that for the double-placebo group, was 1.14 g/dL (95% confidence interval [CI], 0.82-1.47 g/dL) greater for the IPT+iron group, 0.79 g/dL (95% CI, 0.46-1.10 g/dL) greater for the iron group, and 0.17 g/dL (95% CI, -0.15-0.49 g/dL) greater for the IPT group. IPT reduced the incidence of malaria parasitemia and clinic visits, but iron did not. The combination of IPT and iron supplementation was most effective in the treatment of mild anemia. Although IPT prevented malaria, the hematological benefit it added to that of a single dose of SP and bednet use was modest.

Anemia↗
PubMed2003

Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria.

Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance-conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens.

Amodiaquine↗
PubMed2006

Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi.

BACKGROUND: Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight. However, the optimal regimen in the setting of a high prevalence of human immunodeficiency virus (HIV) infection remains unclear. METHODS: In Malawi, where the efficacy of SP for the treatment of malaria in children is decreasing, we conducted a randomized, nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women. RESULTS: Of HIV-positive women, 7.8% who received monthly SP had placental malaria, compared with 21.5% of those who received 2-dose SP (relative risk [RR], 0.36 [95% confidence interval {CI}, 0.17-0.79]). Of HIV-negative women, 2.3% who received monthly SP and 6.3% who received 2-dose SP had placental malaria (RR, 0.37 [95% CI, 0.11-1.19]). Less than 1% of women reported adverse drug reactions, with no increase in HIV-positive women or those who received monthly SP. CONCLUSIONS: In HIV-positive pregnant women, monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria. The study also demonstrates the continued efficacy of SP for the prevention of placental malaria, even in the face of its decreasing efficacy for the treatment of malaria in children. In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection, monthly SP IPTp should be adopted.

Adolescent↗
PubMed2002

Comparison of ion-pairing and ion-suppressing liquid chromatographic methods for the determination of pyrimethamine and ormetoprim in chicken feed.

A high-performance liquid chromatographic (HPLC) method is developed to simultaneously determine pyrimethamine (PYR) and ormetoprim (OMT) in chicken feed. In the ion-pairing HPLC determination of PYR and OMT, the relation between the retention factor (k') and the concentration of the organic phase (acetonitrile) shows a characteristic curve. The k' value first decreases and then increases slowly with increasing concentrations of acetonitrile, but then increases rapidly when the acetonitrile concentration increases to 90%. Resolutions (Rs) of PYR and OMT decrease gradually when the concentration of organic phase increases. Increasing the concentration of the pairing ion sodium 1-octanesulfonate (PIC B-8) can decrease the k' and Rs values. Optimum values of k' and Rs are obtained using 82% acetonitrile in 0.005 M PIC B-8. In ion-suppressing HPLC, varying the concentration of Na2HPO4 has little effect on either the k' or Rs values of PYR or OMT at pH 7.5. However, at pH 4.0, k' and Rs decline when the concentration of Na2HPO4 increases. In general, ion-pairing HPLC generates more satisfactory results than ion-suppressing HPLC. Using 82% acetonitrile in water containing 0.001M PIC B-8 as the mobile phase, linear calibration curves are obtained in the range from 1 to 5 mg/L of PYR and OMT. Sulfamonomethoxine, sulfadimethoxine, sulfaquinoxaline, trimethoprim, amprolium, clopidol, and nicarbazin do not interfere with the detection of PYR or OMT. The recoveries of PYR from spiked feed at 1 and 5 mg/Kg are 73.0% and 72.0%, respectively, and those of OMT from spiked feed at 3 and 7 mg/Kg are 50.3% and 53.6%, respectively.

Animal Feed↗
PubMed2000

Inhibition of growth of Pneumocystis carinii by lactoferrins alone and in combination with pyrimethamine, clarithromycin and minocycline.

The in vitro activity of lactoferrins alone and in combination with clarithromycin, minocycline and pyrimethamine was investigated against three clinical isolates of Pneumocystis carinii. Susceptibility was tested by inoculating isolates on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of each agent. At 20 mg/L, bovine lactoferrin, the most active agent, suppressed the growth of cystic and trophic forms by >60%. Human lactoferrin, at the same concentration, suppressed the growth of cystic and trophic forms by >50%. Lactoferrins at 20 mg/L combined with clarithromycin 4 mg/L had high anti-P. carinii activity, with a >90% decrease in cystic and trophic form counts. Our study suggests that lactoferrins may inhibit P. carinii growth in vitro and act synergically with other clinically used compounds. These findings lend experimental support to the use of iron-chelating agents in the therapy of pneumocystis infections.

Animals↗
PubMed2006

Plasmodium falciparum infection dynamics and transmission potential following treatment with sulfadoxine-pyrimethamine.

OBJECTIVES: To investigate the overall efficacy of sulfadoxine-pyrimethamine (SP) treatment and the corresponding transmission potential for patients infected with SP-resistant Plasmodium falciparum. METHODS: A mathematical model of the in-host dynamics of P. falciparum infections was used to simulate infections with parasites having different numbers of mutations in the dhfr and dhps genes and their responses to SP treatment. The treatment outcome and transmission potential of each simulated infection following SP treatment was assessed by tracking asexual parasite density and the number of days with sufficient mature gametocytes to give a > 95% probability of infecting a mosquito. RESULTS: The results show treatment failure only occurring in patients infected with parasites having two mutations in dihydrofolate reductase (DHFR) combined with at least two mutations in dihydropteroate synthetase (DHPS) or with parasites having a triple mutation in DHFR. Highly mutated parasites (three mutations in each gene) caused the highest clinical failure rate, while moderately mutated parasites (three mutations in DHFR plus one mutation in DHPS) produced a high rate of asymptomatic parasitological failure following SP treatment. This high rate of asymptomatic recrudescence caused the transmission potential of infections with moderately resistant parasites to exceed that of highly resistant parasites. CONCLUSIONS: The model output suggests that infection dynamics following SP treatment and the overall transmission potential are inherently linked. The combination of prolonged asymptomatic parasitaemia and increased transmission potential allows parasites having three mutations in DHFR, but fewer mutations in DHPS, to expand largely unnoticed.

Algorithms↗
PubMed1993

Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients.

OBJECTIVE: To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients. DESIGN: Prospective randomized open trial. SETTING: HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital. PATIENTS: A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis. INTERVENTION: Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85). MAIN OUTCOME MEASURES: Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol. RESULTS: After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity. CONCLUSIONS: At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.

AIDS-Related Opportunistic Infections↗
PubMed1985

Simultaneous estimation of serum concentrations of dapsone, monoacetyldapsone, and pyrimethamine in Chinese men on maloprim for malaria prophylaxis using reversed-phase high performance liquid chromatography.

A reversed-phase high performance liquid chromatography method was developed to simultaneously estimate serum concentrations of dapsone (DDS), monoacetyldapsone (MADDS), and pyrimethamine (PYR) in 34 young adult Chinese men after they had taken the sixth weekly dose of Maloprim for malaria prophylaxis. Serum concentrations of DDS, MADDS, and PYR after 24 h were (mean +/- SEM) 374 +/- 31.3, 310 +/- 30.4, and 121 +/- 7.9 ng/ml, respectively. The 72-h serum concentrations of DDS, MADDS, and PYR were (mean +/- SEM) 134 +/- 21.6, 115 +/- 17.9, and 80 +/- 7.2 ng/ml, respectively. Serum concentrations of DDS and MADDS in many subjects after 120 h were less than 20 ng/ml, while mean +/- SEM concentration of PYR was 53 +/- 5.6 ng/ml. Acetylator phenotyping of the subjects showed that there were 31 (91%) fast acetylators, three (9%) intermediate acetylators, and no slow acetylators.

Acetylation↗
PubMed1991

Quantitation of Fansimef components (mefloquine + sulfadoxine + pyrimethamine) in human plasma by two high-performance liquid chromatographic methods.

Two simple, precise, and selective high-performance liquid chromatographic methods are described for the simultaneous quantitation of mefloquine (MQ) plus pyrimethamine (PYR) or sulfadoxine (SDX) plus its principal metabolite N4-acetylsulfadoxine (N4SDX) in human plasma. After a single-step extraction, MQ plus PYR and SDX plus N4SDX including internal standards were separated using ion-paired and ion-suppression chromatography. Total run times for the assays were less than 12 min. Intraassay and interassay precision of the methods expressed as the coefficients of variation were less than 9% in plasma for the four compounds. The extraction recovery averaged 98% for MQ, 97% for PYR, 96% for SDX, and 81% for N4SDX. Plasma concentrations of the four compounds in a pediatric patient after a single oral dose of Fansimef (MQ + SDX + PYR) were determined to demonstrate the clinical application of the methods.

Antimalarials↗