Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Proguanil”

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
PubMed2000

Simultaneous separation of atovaquone, proguanil and its metabolites on a mixed mode high-performance liquid chromatographic column.

An isocratic high-performance liquid chromatographic (HPLC) method for simultaneous separation of the components in the antimalarial combination drug Malarone with UV detection is described. An HPLC system using a mixed mode column composed of 50% C(18) phase and 50% strong cation-exchanger has been optimised for the simultaneous separation of atovaquone, proguanil and its two main metabolites. The mobile phase was optimised for factors such as pH, counter ion concentration and acetonitrile. Elimination of interferences from other antimalarial drugs was achieved by adding sodium perchlorate to the mobile phase. With a mobile phase of acetonitrile-phosphate buffer (60:40, v/v) pH 6.8, 50.7 mmol l(-1) K+ and 10 mmol l(-1) Na x ClO4, separation was achieved within a run time shorter than 17 min.

Acetonitriles↗
PubMed2002

Dual-mode gradient HPLC procedure for the simultaneous determination of chloroquine and proguanil.

In order to assay the antipaludic capsule of the Service de Santé des Armées (SSA), that contains two antimalarial drugs, i.e. chloroquine sulfate (CQS, cp1) and proguanil hydrochloride (PGH, cp5), a HPLC procedure was developed. A reversed-phase ion-pair high-performance liquid chromatography (HPLC) method with an ultraviolet detection at 254 nm was set up and validated. Elution system includes programming of both organic concentration and flow-rate known as 'dual-mode gradient'. This method allows the simultaneous determination of both active compounds and separation of four process related substances. The method is simple, rapid, selective and accurate, and the precision is good with an inter- and intra-assay of <2%. The sensitivity is particularly suitable for pharmaceutical quality control.

Antimalarials↗
PubMed1997

Optimisation of the reversed phase liquid chromatographic separation of atovaquone, proguanil and related substances.

The optimisation of the separation of the antimalarial drugs, proguanil and atovaquone and six related compounds was obtained by two independent optimisation steps; the optimisation of the mobile phase composition and the optimisation of the pH. This was done using window selection diagrams (WSD) and a mixture design. The optimal conditions allow the identification of the six related compounds down to 0.1%.

Antimalarials↗
PubMed2006

[Retrospective analysis of 107 imported adult cases of malaria. Experience report of uncomplicated falciparum malaria treatment in adults with oral atovaquone-proguanil].

OBJECTIVES: The principal aim of this study was to assess the efficacy of the combination of oral atovaquone and proguanil (AP) in routine treatment of uncomplicated falciparum malaria in recent visitors to the tropics. We also analyzed the epidemiologic, clinical and hematologic characteristics of these patients with imported malaria. METHODS: This retrospective study reviewed the records of 107 cases of imported malaria, treated in the Tropical Disease Unit of Bordeaux University Hospital (France). RESULTS: More than 75% had uncomplicated falciparum malaria; 10 developed complications, and one died. Average time from fever onset to first medical consultation was 4.8 days. Less than 10% had used physical measures of prevention against mosquito bites, and nearly 65% had not used chemoprophylaxis. The most frequent hematologic abnormalities were eosinopenia (84%) and thrombocytopenia (75%). In more than 30% of cases, another disease was also present. The oral AP combination was administered to more than 86% of patients with uncomplicated falciparum malaria (n=72). Tolerance was excellent and only one treatment failure was observed, associated with digestive disorders. CONCLUSION: Better information for travelers and general practitioners is required to reduce the number of cases of imported malaria and to shorten the delay between symptom onset and specific treatment. The oral AP combination appears to be a safe and effective treatment for uncomplicated imported falciparum malaria.

Administration, Oral↗
PubMed2002

Effect of proguanil interaction on bioavailability of cloxacillin.

METHODS: To investigate a potential drug-drug interaction between proguanil (PG) and cloxacillin (Clox). Seven healthy adult volunteers received a single oral dose of Clox plus coadministration of single oral doses of PG and Clox in a simple cross-over manner after a wash-out period of 1 week. Total urine voided was collected at predetermined time intervals over 12 h. Amount of Clox in urine was determined by a reversed-phase high-pressure liquid chromatography method. RESULTS: The mean maximum excretion rate [(dDu/dt)max] of Clox when taken alone was 16.13 +/- 2.92 mg/h at tmax of 1.86 +/- 01.07 hours, whereas in the presence of PG, it was 7.72 +/- 3.24 mg/h at tmax of 2.43 +/- 00.98 hours (P < 0.0001). The total amount of Clox excreted in urine (Du infinity) in 12 h was markedly reduced by coadministration with PG by up to 48% with Du infinity of 49.57 +/- 8.16 mg after Clox alone and 25.81 +/- 8.46 mg in the presence of PG (P < 0.0001). The tmax and t1/2-values obtained from the excretion rate plot were lengthened by 23 and 34%, respectively, in the presence of PG but the differences were not statistically significant (P > 0.05). CONCLUSION: These pharmacokinetic values indicate slowed and diminished absorption (bioavailability) of Clox when concurrently administered with PG. The clinical implication is unknown. However, concomitant administration of the two drugs during antibacterial therapy should be done with caution so as to avoid subtherapeutic levels of Clox, which can lead to treatment failure and facilitate drug resistance.

Administration, Oral↗
PubMed1997

Compliance with and tolerance of mefloquine and chloroquine + proguanil malaria chemoprophylaxis in French short-term travellers to sub-Saharan Africa.

To compare the compliance with and tolerance of mefloquine (MQ) and chloroquine + proguanil (CQ-PRO) chemoprophylaxis, we conducted a study using a self-reported questionnaire in 2 groups of native French adult visitors to Senegal or Kenya. CQ (100 mg daily) + PRO (200 mg daily) prophylaxis was prescribed for all patients travelling to Senegal and for those going to Kenya when MQ was contraindicated; MQ (250 mg weekly) was prescribed for the other subjects. There were no significant differences in age, sex, exposition and measures of protection against mosquito bites, concomitant drug use or mean duration of chemoprophylaxis between the 2 groups, and compliance during travel was excellent in both. Chemoprophylaxis was more frequently interrupted prematurely in the MQ group. The rates of overall side-effects attributed to malaria chemoprophylaxis were 16% for MQ against 12% CQ-PRO (not significant). However, nonserious neuropsychiatric adverse events are more frequent with MQ: 11.5% compared to 2% with CQ-PRO. MQ should be used with caution.

Adult↗
PubMed2002

Tolerability of doxycycline monohydrate salt vs. chloroquine-proguanil in malaria chemoprophylaxis.

The resistance of Plasmodium falciparum to the chloroquine-proguanil association (C/P) as antimalarial chemoprophylaxis is becoming increasingly common in Africa. Daily oral doxycycline hyclate 100 mg is effective as malaria prophylaxis. But the hyclate salt's adverse effects combined with the capsule's galenic form are incompatible with good chemoprophylaxis compliance. We conducted a randomized group study of 522 French soldiers deployed in Gabon and Chad for 4 months to determine the tolerability of short-term malaria chemoprophylaxis with a 100-mg daily tablet of a monohydrate doxycycline salt compared with a daily C/P capsule. At days 7 and 120, compliance was better in the doxycycline group [respectively 98.5%vs. 73.9% (P < 0.001) and 90.5%vs. 74% (P < 0.001)]. No major event (evacuation, hospitalization) was related to the medications. Epigastralgia, diarrhoea, urticaria, mouth ulcers, sun sensitization and desquamation were significantly more frequent in the C/P group (P < 0.05). There was no statistical difference for malaria incidence, vertigo, nausea and hair loss. These results suggest that doxycycline monohydrate may be safely used in short-term malaria chemoprophylaxis. With the same efficacy as a hyclate doxycycline, doxycycline monohydrate could be a good chemoprophylaxis for short-term travellers at particular risk of C/P resistant P. falciparum malaria.

Adult↗
PubMed1977

Experimental studies of the potentiation of proguanil and pyrimethamine by dapsone using Plasmodium berghei in white mice.

An accurate system with stringent criteria has been established to test antimalarial drugs and drug combinations against Plasmodium berghei in mice. Minimum effective doses for a number of antimalarial drugs have been determined when used in this system. Considerable potentiation of the activity of pyrimethamine and to a somewhat less extent of proguanil by dapsone has been demonstrated. The need to extend studies of these combinations to the parasites of human malaria is discussed in terms of establishing a safe chemoprophylactic regime in the presence of drug-resistant strains of parasites.

Animals↗
PubMed2003

Atovaquone and proguanil versus amodiaquine for the treatment of Plasmodium falciparum malaria in African infants and young children.

Malaria-related morbidity and mortality are greatest among young children in areas with high malaria transmission intensity. An open-label, randomized study was done to evaluate the efficacy and safety of the combination of atovaquone and proguanil formulated as pediatric-strength tablets (20 and 8 mg/kg of body weight, respectively, administered once daily for 3 days), compared with amodiaquine (10 mg/kg of body weight, once daily for 3 days), among children weighing > or =5 and <11 kg in Gabon. Two hundred patients aged 3-43 months were recruited. Use of atovaquone/proguanil resulted in a cure rate on day 28 of 95% (87 of 92 children), compared with 53% (41 of 78 children) for amodiaquine (difference, 42%; 95% CI, 30%-54%; P<.001). The incidence of adverse events was similar in both groups, and no serious adverse events were attributed to the use of atovaquone/proguanil. Atovaquone/proguanil was found to be highly effective and safe for the treatment of Plasmodium falciparum malaria in infants and young children weighing 5-10 kg in Africa.

Amodiaquine↗
PubMed2005

A randomized comparison of artesunate-atovaquone-proguanil versus quinine in treatment for uncomplicated falciparum malaria during pregnancy.

BACKGROUND: There is no safe, practical, and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum. METHODS: We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a randomized, open-label trial with a restricted sequential trial design of 7 days of supervised quinine (SQ7) versus 3 days of artesunate-atovaquone-proguanil (AAP). RESULTS: Eight-one pregnant women entered the study between December 2001 and July 2003; 42 were treated with SQ7 and 39 were treated with AAP. Fever, parasite clearance, and duration of anemia were significantly better with AAP; the treatment failure rate was 7 times lower (5% [2/39] vs. 37% [15/41]; relative risk, 7.1 [95% confidence interval, 1.7-29.2]; P = .001). There were no significant differences in birth weight, duration of gestation, or congenital abnormality rates in newborns or in growth and developmental parameters of infants monitored for 1 year. CONCLUSION: AAP is a well-tolerated, effective, practical, but expensive treatment for multidrug-resistant falciparum malaria during the second or third trimesters of pregnancy. Despite the small number of subjects, our results add to the growing body of evidence that AAP is safe for the mother and the fetus.

Adolescent↗
PubMed1991

The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin oxidation polymorphism--a panel study.

The activation of the antimalarial drug proguanil (PG) to the active metabolite cycloguanil (CG) has been evaluated in a panel of 18 subjects. These subjects had previously been screened and classified as mephenytoin poor (PMm) or extensive metabolisers (EMm) and sparteine poor (PMs) or extensive metabolisers (EMs). Five subjects had the phenotype PMm/EMs, one was PMm/PMs, six subjects were EMm/PMs and six were EMm/EMs. The PG/CG ratio in urine (8 h) was significantly higher in PMm than in EMm (P = 0.0013). This study shows that the P450-isozyme involved in the polymorphic oxidation of mephenytoin is of critical importance in the activation of PG to CG and this may explain the large intersubject variability in CG concentrations in man. PMm make up about 3% of Caucasians, but up to about 20% of Orientals. From the present study, it may be anticipated that the antimalarial effect of PG is absent or impaired in this phenotype. The sparteine polymorphism appeared not to influence the activation of PG to CG significantly.

Adult↗
PubMed1995

Metabolic disposition of proguanil in extensive and poor metabolisers of S-mephenytoin 4'-hydroxylation recruited from an Indonesian population.

1. The metabolism of proguanil (PG) was studied by measuring PG, cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) in plasma and urine samples after an oral 200 mg dose of PG hydrochloride administered to 14 extensive (EMs) and 10 poor hydroxylators (PMs) of S-mephenytoin of Indonesian origin. 2. The mean ( +/- s.d.) values of the elimination half-life (t 1/2) and AUC of PG were significantly (P < 0.01) greater in the PM than in the EM group (20.6 +/- 3.1 vs 14.6 +/- 3.5 (95% confidence intervals of difference 3.1 to 8.9) h; and 5.43 +/- 1.89 vs 3.68 +/- 0.83 (0.58 to 2.91) micrograms ml-1 h). 3. Plasma concentrations of CG, an active metabolite, could not be detected in all PMs, and those of CPB were sufficiently high to determine a time-course in only four PMs. Mean AUC(0,24 h) values of CPB were significantly (P < 0.05) lower in the PM (n = 4) than in the EM group (n = 14) (0.47 +/- 0.13 vs 0.88 +/- 0.50 (-0.14 to 0.96) micrograms ml-1 h). 4. Log10 percentage urinary recovery of 4'-hydroxymephenytoin correlated significantly (P < 0.05) with the t 1/2 (rs = -0.661) and AUC (rs = -0.652) of PG. 5. PG, CG and CPB were detectable in urine at 12 h in all subjects. Log10 percentage urinary recovery of 4'-hydroxymephenytoin correlated significantly (P < 0.01) with urinary PG/CG (rs = -0.876), PG/CPB (rs = -0.833) and PG/(CG + CPB) (rs = -0.831) metabolic ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Prolonged malaria prophylaxis with chloroquine and proguanil (chloroguanide) in a nonimmune resident population of an endemic area with a high prevalence of chloroquine resistance.

One hundred thirty nonimmune subjects living in Yaoundé, Cameroon, completed an 18-month prospective study on the efficacy and safety of weekly chloroquine and daily proguanil (chloroguanide) (Ch-P) in malaria prevention. A total of 9 of 78 Ch-P-treated subjects and 26 of 52 subjects who received no prophylaxis contracted Plasmodium falciparum infection during this period (P less than 0.00005). These two groups were comparable for demographic parameters and degree of exposure. Clinical manifestations were of similar severities in the two groups, but parasite counts were significantly higher in the subjects who received no prophylaxis (P less than 0.00005). Side effects of prophylaxis were frequent (31%), minor, and related to chloroquine, and they usually resolved within 4 to 6 weeks. Prolonged administration of Ch-P is safe and effectively prevents P. falciparum malaria in an endemic area with a high prevalence of chloroquine resistance.

Adult↗
PubMed1988

Malaria chemoprophylaxis with a proguanil-chloroquine-maloprim combination in Papua New Guinea.

Proguanil 200mg daily and chloroquine base 300mg weekly along with maloprim 1 tablet weekly was used as malaria chemoprophylaxis for 140 Hong Kong based soliders on a seven-week jungle exercise in a holoendemic malarial area of Papua New Guinea. On return from exercise all personnel were treated with primaquine 7.5mg three times daily for a two week period. One solider developed P. falciparum on the exercise whilst taking chemoprophylaxis and four subsequently developed P. vivax malaria after cessation of chemoprophylaxis.

Animals↗
PubMed1994

Evaluation of WR250417 (a proguanil analog) for causal prophylactic activity in the Plasmodium cynomolgi-Macaca mulatta model.

The Plasmodium cynomolgi-Macaca mulatta model has been used to test the antimalarial activity of new drugs for both radical cure and casual prophylaxis. The proguanil analog WR250417 (also known as PS-15) was evaluated for causal prophylactic activity in rhesus monkeys infected with P. cynomolgi bastianelli. Four monkeys were orally dosed with 40 mg/kg/day of WR250417 over three days (-1, 0, and +1). Sporozoite-induced infection of P. cynomolgi was initiated on day 0 with 1 x 10(6) sporozoites to each monkey. Compound WR250417 extended the prepatent period from an average of 8.5 days for controls (n = 2) to a mean of 18.3 days (range 18-19 days, n = 4) for drug-treated monkeys. Analysis of plasma drug concentrations by high-performance liquid chromatography showed that the monkeys converted the WR250417 to its putative principal active metabolite WR99210 (a dihydrotriazine). These findings demonstrate that WR250417 and its principal metabolite do not prevent primary infection by P. cynomolgi.

Administration, Oral↗
PubMed1995

Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa.

As chloroquine resistance spreads across Africa, the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and proguanil are being used as alternative first-line drugs for the treatment and prevention of Plasmodium falciparum malaria. Resistance to these drugs is conferred by point mutations in parasite DHFR. These point mutations can be detected by polymerase chain reaction (PCR) assays, but better methods for sample collection, DNA extraction, and a diagnostic PCR are needed to make these assays useful in malaria-endemic areas. Here we report methods for collecting fingerstick blood onto filter paper strips that are air-dried, then stored and transported at room temperature. Cell lysis and DNA extraction are accomplished by boiling in Chelex-100. We also report a nested PCR technique that has improved sensitivity and specificity. These procedures readily detect mixed infections of parasites with both sensitive and resistant genotypes (confirmed by direct sequencing) and are reliable at parasite densities less than 250/mm3 in field surveys.

Animals↗
PubMed1996

Simultaneous measurement of proguanil and its metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography, and its preliminary application in relation to genetically determined S-mephenytoin 4'-hydroxylation status.

A simple high-performance liquid chromatographic (HPLC) assay method was developed for the measurement of proguanil (PG) and its major metabolites, cycloguanil (CG) and 4-chlorophenyl-biguanide (CPB), in human plasma and urine. The assay allowed the simultaneous determination of all analytes in 1 ml of plasma or 0.1 ml of urine. The detection limits of PG, CG, and CPB, defined as the signal-to-noise ratio of 3, were 1 and 5 ng/ml for plasma and urine samples, respectively. Recoveries of the analytes and the internal standard (pyrimethamine) were > 62% from plasma and > 77% from urine. Intra-assay and interassay coefficients of variation for all analytes in plasma and urine were < 10% except for the values of CG and CPB, which ranged from 10% to 15% at one or two concentrations among 4-5 concentrations studied. The clinical applicability of the method was assessed by the preliminary pharmacokinetic study of PG, CG, and CPB in six healthy volunteers with the individually known phenotypes (extensive and poor metabolizers) of S-mephenytoin 4'-hydroxylation, suggesting that individuals with a poor metabolizer phenotype of S-mephenytoin have a much lower capacity to bioactivate PG to CG compared with the extensive metabolizers.

Adult↗
PubMedDate not supplied

Atovaquone plus proguanil versus halofantrine for the treatment of imported acute uncomplicated Plasmodium falciparum malaria in non-immune adults: a randomized comparative trial.

In endemic zones, the atovaquone-proguanil (AP) combination is well tolerated and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multicenter open-label trial to determine the efficacy and tolerability of the AP combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programmed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patients enrolled in the study, 41 were assessable for the cure rate (21 in the AP group and 20 in the HF group). All the patients were cured. The mean parasite clearance time was longer (63+/-23 hours) in the AP group than in the HF group (48+/-15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiographic changes were observed, particularly in the QTc interval. The AP combination appears to be a valuable alternative treatment in non-immune adults.

Acute Disease↗