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Biomedical subjects

D Bunnag

Publications and source records attributed to D Bunnag.

At least 37 records · Page 2Linked to original sources
PubMed1993

Mefloquine level monitoring in patients with multidrug resistant Plasmodium falciparum on the Thai Myanmar border.

A total of 42 patients with uncomplicated falciparum malaria who attended the malaria clinic in Mae Sot, Tak Province were treated with single oral dose of MSP 3 tablets (Fansimef, equivalent to 750 mg of mefloquine) concurrently with primaquine (30 mg). They all contracted the infection from Cambodia. The aim of the study was to monitor the efficacy of MSP 3 tablets for the treatment of this highly multiple drug resistant strains of Plasmodium falciparum in this area. Of the 39 patients included for efficacy assessment, 13 (33.3%) patients had sensitive responses, whereas 15 (38.5%) and 8 (20.5%) had RI and RII types of response, respectively. Melfoquine concentrations on Day-3 after treatment in patients with sensitive and treatment failure groups were comparable; the respective mean (SD) values were 665 (279) and 772 (264) ng/ml.

Administration, Oral↗
PubMed1993

Mefloquine monitoring in acute uncomplicated malaria treated with Fansimef and Lariam.

Mefloquine levels were compared between Plasmodium falciparum malaria patients with sensitive response and those with treatment failure who received 3 drug regimens of mefloquine (46 patients with MSP 3 tablets (Fansimef), 38 and 34 with mefloquine (Lariam) 750 mg and 1,250 mg). Mefloquine concentrations on Day-1 in any regimens in patients with treatment failure were significantly lower than those from the sensitive response, whereas there was no difference in the concentrations on Day-7. However, MIC values of mefloquine prior to drug treatment were comparable in both groups. The study suggests that pre-treatment in vitro sensitivity testing was a non-reliable indicator of clinical outcome. Mefloquine concentration on the first day after treatment is a better predictor of the treatment outcome.

Acute Disease↗
PubMed1993

Mefloquine levels in patients with mefloquine resistant Plasmodium falciparum in the eastern part of Thailand.

A total of 99 patients with uncomplicated falciparum malaria who attended the malaria clinic in Bo Rai, Trat Province were treated with a single oral dose of MSP 3 tablets (Fansimef; equivalent to 750 mg of mefloquine) concurrently with primaquine (30 mg). The aim of the study was to detect RII and RIII types of response with 3 tablets of MSP. Seven (8.1%) and 22 patients (25.3%) had RII and RIII types of response, respectively, and 58 (66.8%) had no parasitemia on Day-7 (S or RI response). Mefloquine concentrations on Day-3 after treatment in patients in the S/RI group were significantly higher than those with early treatment failure (RII, RIII), with the respective mean (SD) values of 1,959 (696) and 1,622 (863) ng/ml. The mean concentrations of mefloquine in these patients with RII and RIII types of response were higher than those with a sensitive response in a previous study. The result suggests that Plasmodium falciparum strains in this part of the country are highly resistant to mefloquine and that blood levels of mefloquine on Day-3 may also be a good indicator of treatment outcome in this particular area.

Adolescent↗
PubMed1993

Clinical trials with halofantrine in acute uncomplicated falciparum malaria in Thailand.

The antimalarial efficacy of halofantrine was compared with mefloquine in an open-label, randomized comparative trial in adult male patients with acute uncomplicated falciparum malaria. Twenty-eight patients received halofantrine and 27 received mefloquine. Halofantrine was administered in 3 doses of 500 mg at 6 hour intervals and mefloquine was administered in divided doses of 1,250 mg or 1,500 mg depending on whether the patients weighed less than or more than 60 kg. The patients were followed for 42 days and observed for drug tolerance and evidence of recrudescence. Response to treatment was favorable with both drugs, but three patients (two treated with halofantrine and one with mefloquine) did not completely eliminate malaria parasites from peripheral blood films in seven days. The parasite and fever clearance times were 75.6 and 55.7 hours, and 80.1 and 61.3 hours, respectively for halofantrine and mefloquine. However, 12 patients recrudesced during the 42 day follow-up period. Nine of these had been treated with halofantrine and three with mefloquine. The 42-day cure rate for the two drugs was 56% and 84%, respectively. The side-effects of halofantrine and mefloquine were comparable and transient. These are diarrhea, dizziness, orthostatic hypotension and black out. However, vomiting was found to be more common in mefloquine group (41% vs 22%).

Adolescent↗
PubMed1993

Intramuscular artemether in female patients with uncomplicated falciparum malaria.

Thirty-three female patients suffering from acute uncomplicated falciparum malaria were treated with intramuscular artemether for 5 days during May-October 1990. Fourteen patients received 160 mg as an initial dose, followed by 80 mg daily for 4 days. Nineteen patients with low body weight (mean weight of 36.5 kg) were given artemether at 3.2/kg as a loading dose and followed by 1.6 mg/kg/dose for another 4 days. The geometric mean of parasitemia was 17,378/microliters (range 640-234,720). The mean fever (FCT) and parasite clearance time (PCT) were 41.8 and 49.4 hours, respectively. Two patients had probable intercurrent infection with FCT of over 7 days. Thirty-one patients had completed the 28-day follow-up. The cure rate was 90.3% (28/31). Three patients had RI type of response. Mild and transient adverse effects were experienced in eleven patients; these consisted of pain at the injection sites, vomiting, dizziness, abdominal pain, palpitation and diarrhea. These symptoms may in part be due to symptom complex of malaria. The MIC of chloroquine, quinine, quinidine and mefloquine was performed in all patients but only 25 isolates were successfully cultured and tested. The MIC of all tested drugs were shown to be higher than that of previous studies, suggesting that there is a rapid increase of mefloquine resistant strains of falciparum malaria. In conclusion, artemether proves to be effective against multiple drug resistant falciparum malaria (including mefloquine resistant strains) and can be considered as an alternative antimalarial to mefloquine. The drug was well tolerated in female patients with mild and transient side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

A comparison of the pharmacokinetic and pharmacodynamic properties of quinine and quinidine in healthy Thai males.

1. Eight healthy Thai males, aged 19-27 years, received quinine or quinidine dihydrochloride 10 mg kg-1 body weight by intravenous infusion over 1 h. At least 1 week later, the alternative alkaloid was administered. 2. The terminal elimination half-time of quinidine was shorter than that of quinine (median [range]; 5.7 [5.0-10.0] vs 9.9 [8.8-15.1] h, P < 0.01), the volume of distribution at steady state (Vss) for quinidine was larger than that for quinine (3.5 [2.5-5.6] vs 3.1 [1.8-4.1] 1 kg-1; P = 0.02) and quinidine was less bound to plasma proteins (% free drug: 22.8 [15.4-47.2] vs 9.4 [7.3-15.0]%, P < 0.01). Total clearance was greater for quinidine (7.7 [3.9-11.4] vs 3.4 [1.8-4.6] ml min-1 kg-1, P < 0.01) but not for clearance of unbound drug (32.2 [14.6-50.4] vs 29.9 [20.2-50.9] ml min-1 kg-1 respectively, P > 0.2). 3. Side-effects, including transient hypotension after quinidine in two cases, were mild. 4. Both drugs produced prolongation of the rate-corrected QT interval (QTc), with similar rates of elimination from the cardiac conduction 'effect' compartment (keo; 4.14 [0.03-15.33] h-1 for quinine, 3.74 [1.63-13.14] h-1 for quinidine, P > 0.19). Using a linear concentration-response model, the intercept ('threshold') for quinidine effect was lower than that for quinine (P = 0.004) but the slopes (change in QTc for a given change in free drug concentration) were similar (P = 0.56).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria.

Plasmodium falciparum malaria in Thailand is highly resistant to available antimalarials, and alternative drugs are needed urgently. Artemether is effective against falciparum malaria but associated with a high recrudescence rate. The proper dosage regimen remains to be defined. We have done a clinical trial comparing mefloquine 1250 mg in divided doses with oral artemether at 700 mg total dose given over 5 days in acute uncomplicated falciparum malaria. 46 patients, admitted to the Bangkok Hospital for Tropical Diseases, were randomised to receive either mefloquine (12) or artemether (34). Hospital follow-up was 28 days for the artemether group and 42 days for the mefloquine group. Oral artemether gave a significantly faster parasite clearance time than mefloquine (30 vs 64 h), and a significantly better cure rate (97 vs 64%) with fewer episodes of dizziness and vomiting. Oral artemether at 700 mg given over 5 days is effective and well tolerated. The cure rate with this regimen is higher than that reported by previous studies with 600 mg intramuscular artemether given over 5 days. Oral artemether can be considered as an alternative drug for multiple-drug-resistant falciparum malaria.

Acute Disease↗
PubMed1992

Effect of tetracycline on mefloquine pharmacokinetics in Thai males.

The kinetics of a single oral dose of mefloquine given either alone or with tetracycline has been studied in 20 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with tetracycline (1600 vs 1160 ng.ml-1), as well as a significantly reduced terminal half-life (14.4 vs 19.3 days), mean residence time (11.9 vs 16.0 days) and volume of distribution at steady state (13.3 vs 19.9 1.kg-1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 7 days was significantly increased by tetracycline (6.18 vs 4.76 micrograms.ml-1.day). The changes in mefloquine disposition after tetracycline treatment are probably due to a reduction in enterohepatic recycling. The initial increase in mefloquine AUC without an apparent increase in side-effects suggests that this combination may have a place in the treatment of multi-drug resistant falciparum malaria.

Adult↗
PubMed1992

Plasmodicidal effect of desferrioxamine B in human vivax or falciparum malaria from Thailand.

Desferrioxamine B (DFO, Desferal), an iron chelator, was earlier shown to be active against Plasmodium falciparum in vitro and in vivo. The present open pilot study served to assess its clinical tolerability and efficacy in human malaria under hospital conditions. Continuous intravenous DFO was administered to 28 Thai males at a dose of 100 mg/kg over 24 h for 3 consecutive days. No other antimalarial therapy was administered unless recrudescence had occurred. The first 14 patients had symptomatic Plasmodium vivax (P.v.) malaria, while the other 14 patients were suffering from uncomplicated Plasmodium falciparum malaria (P.f.). Both groups were treated in Bangkok, where malaria transmission does not take place, and followed up, on the ward, for 3 weeks (P.v. group) or 4 weeks (P.f. group) after the start of therapy. In both groups DFO reduced the parasitaemia to zero within 106 and 57 h respectively. The fever clearance time was 55 and 60 h, respectively. The overall tolerability of DFO was good but 4 P.v. and 5 P.f. patients had transient visual blurring. Recrudescences were observed on average 15, respectively 10 days after the start of therapy. Only 2 P.v. patients and none of the P.f. patients remained free of recrudescences during the observation period. There was no apparent gametocytocidal effect of DFO on P.f.

Adult↗
PubMed1992

Two-site sandwich ELISA for detection of Plasmodium vivax blood stage antigens using monoclonal and polyclonal antibodies.

Two systems of sandwich enzyme-linked immunosorbent assay (ELISA), a two-site monoclonal antibody sandwich ELISA MAb-MAb sandwich ELISA) and a two site polyclonal-monoclonal antibody sandwich ELISA (PAb-MAb sandwich ELISA) for the detection of Plasmodium vivax antigens were developed. The assays showed good correlation with the level of parasitemia when tested against serially diluted P. vivax parasites (r = 0.937, and 0.997 for MAb-MAb and PAb-MAb sandwich ELISA, respectively), with the ability to detect as few as 6.68 parasites/10(6) erythrocytes and 2.69 parasites/10(3) erythrocytes, respectively. The MAb-MAb sandwich ELISA was specific, since it was positive only with P. vivax-infected erythrocytes from vivax malaria patients and negative when erythrocytes from 34 healthy individuals and 30 falciparum malaria cases were tested. In contrast, cross-reaction was found in the PAb-MAb sandwich ELISA when the plates were coated with polyclonal IgG and tested against the serially diluted P. falciparum SO strain antigen prepared from in vitro cultures. Comparison between the two systems of two-site sandwich ELISA showed that the MAb-MAb sandwich ELISA was superior to the PAb-MAb sandwich ELISA: (1) it gave a higher sensitivity when tested with serially diluted P. vivax antigen preparations from vivax malaria patients; (2) it gave a higher specificity when tested with the SO strain of P. falciparum from in vitro cultures, (3) it gave a lower absorbance value when tested with erythrocytes from healthy individuals. All 281 cases of vivax malaria already proven by microscopic examination were positive by MAb-MAb sandwich ELISA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Artemether in the treatment of multiple drug resistant falciparum malaria.

Artemether has the potential to be an alternative antimalarial for multiple drug resistant falciparum malaria. However, it has been associated with high recrudescent rates which may be due to incorrect dosage regimens. The dosage regimens are varied from country to contry. We have carried out a comparative study of two dosage regimens, ie 480 mg and 600 mg total dose given over 5 days in uncomplicated and severe falciparum malaria. 167 patients were included in the study, 61 with acute uncomplicated falciparum malaria and 106 with severe malaria. All patients showed a good initial response. The difference in total dose had no effect on the parasite or fever clearance time (PCT or FCT). However, the severity of the disease did have some influence of these times. The PCT and FCT from either regimen of uncomplicated malaria were significantly faster than those of severe malaria (p < 0.005 and = 0.05, respectively). The cure rate seems to have some correlation with the amount of drug given and severity of the disease. The cure rates in uncomplicated malaria were 84 and 92%, respectively, for 480 mg and 600 mg. In severe malaria the cure rates dropped to 65 and 76%, respectively, for 480 and 600 mg. We conclude that artemether can be considered as an alternative antimalarial for multiple drug resistant falciparum malaria. However, the cure rate of severe falciparum malaria in this study is not considered satisfactory in areas with multiple drug resistant falciparum malaria. Further studies are needed to assess the curative efficacy with different dosage regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Preliminary report: a comparative clinical trial of artemether and quinine in severe falciparum malaria.

Twenty-six patients with severe falciparum malaria were randomized to be treated with quinine or artemether. Twelve patients received quinine at the standard dose and fourteen patients received artemether intramuscularly at a total dose of 640 mg over 7 days. The patients were kept in the hospital for at least 7 days. Peripheral smear was performed 6-hourly until there was no parasitemia, then daily until discharged. Adverse effects were monitored through physical examination, laboratory findings and questionnaires. Laboratory examination was performed on admission, day 2, day 4 weekly until discharged. The patients in both groups were comparable in age, body weight, admission parasitemia, hemoglobin and white blood cell count. The survival rates were 93% and 58% in artemether and quinine groups, respectively (p = 0.052 at 95% confidence, using Fisher's exact test). The parasite and fever clearance times, and the time taken to gain consciousness in cerebral malaria patients were not significantly different between the two groups. Adverse effects in the quinine group consisted of dizziness and vertigo which were found in 4 patients. No adverse effects were noticed in the artemether group. This preliminary report suggests that artemether is a good alternative drug for severe falciparum malaria and seems to be better than quinine regarding survival rate and side effects. Confirmation of these findings in a larger study size is needed.

Acute Kidney Injury↗
PubMed1992

Pharmacokinetics of quinine, quinidine and Cinchonine when given as combination.

Pharmacokinetics of quinine, quinidine and cinchonine when given as a combination were evaluated in Thai patients with falciparum malaria during acute infection and convalescence. The combination of quinine, quinidine and cinchonine was randomly given to thirteen patients at 400 mg or 600 mg (consisting of one-third of each component; 7 patients were enrolled in 400 mg regimen and 6 in 600 mg regimen) intravenously every 8 hours for 7 days. The drug combination was given again at day 35 to define the pharmacokinetics of each drug during convalescence. All patients with the 600 mg regimen had good response with 100% cure rate while patients with the 400 mg regimen had a good initial response but one patient recrudesed on day 46. This particular patient had plasma concentrations of all three drugs lower than the mean values of patients with sensitive responses. The plasma levels of quinine and quinidine obtained from the present study were higher than that expected from one-third of the conventional dose (600 mg) when given alone, suggesting drug combination interaction. The terminal half-lives of each of the three components were prolonged during acute malaria when compared to those obtained during convalescence.

Adult↗
PubMed1992

Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial.

At a time when Fansimef, the fixed combination of mefloquine, sulfadoxine and pyrimethamine was considered for prophylaxis of falciparum malaria, a randomized double-blind study comparing the efficacy and tolerability of Fansimef with that of Lariam (mefloquine), Fansidar, chloroquine and placebo in malaria prophylaxis was performed in Thailand from July 1987 to January 1988. The study population of 602 adult males was recruited in Pak Tongchai District, some 360 km North-East of Bangkok, where multiresistant P. falciparum is endemic. All active treatments and placebo were given once weekly for 24 weeks with doses as follows: Fansimef: 125 mg mefloquine + 250 mg sulfadoxine + 12.5 mg pyrimethamine (1 half-strength tablet); Lariam: 125 mg mefloquine (1 half-strength tablet); Fansidar: 500 mg sulfadoxine + 25 mg pyrimethamine; chloroquine; 300 mg. A loading dose of 2 half-strength tablets was given in the Fansimef group in weeks 1 and 2 and in the Lariam group in weeks 1 to 4. The incidence of acute episodes of P. falciparum per 100 person months of prophylaxis was 0.17 each in the Fansimef and the Lariam groups, 1.18 in the Fansidar group, 0.69 in the chloroquine group and 0.64 in the placebo group (differences statistically not significant). Clinically adverse events were reported by 170 subjects (Fansimef 28, Lariam 29, Fansidar 41, choroquine 43, placebo 29; differences statistically not significant). The most frequent adverse events in all groups were headache, sleepiness, dizziness and weakness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Clinical trials of mefloquine with tetracycline.

A comparative trial of the combination of mefloquine or MSP with tetracycline was carried out in fifty-one adult Thai male patients with acute falciparum malaria. The patients were randomized to receive either the combination of tetracycline (250 mg qid for 7 days) with mefloquine 4 tablets (1,000 mg) or with MSP 4 tablets (one tablet contains 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine). Fifty patients had a complete 28-day follow-up period. Both regimens produced similar efficacy with no difference in adverse effects. In the mefloquine plus tetracycline group, the cure rate was 72% (18/25). One patient had an RIII response, the others showed initial response to the treatment with FCT and PCT of 40.7 +/- 27.4 and 76.2 +/- 34.2 hours (mean +/- SD) respectively. However, 6 patients developed recrudescence between days 17 and 29 (RI), 3 of these had vomiting. In the MSP plus tetracycline group, the cure rate was 76% (19/25). The means (+/- SD) of FCT and PCT were 44.7 +/- 38.0 and 80.6 +/- 25.0 hours, respectively. Six patients had recrudescence between days 17 and 31 (RI), 2 of these had vomiting. Although the addition of tetracycline improved the cure rate of mefloquine when compared with standard dose of mefloquine alone (3 tablets), these combinations seem to be useful in areas where alternative drugs are not available.

Acute Disease↗
PubMed1992

Thrombocytopenia in malaria.

The relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with Plasmodium falciparum malaria and 12 patients with P. vivax malaria. Platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- SD) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes in counts and either indirect or direct platelet antibody levels. These findings suggest that a non-immunologically mediated mechanism is involved in the pathogenesis of thrombocytopenia in malaria.

Adolescent↗
PubMed1992

Effect of mefloquine on electrocardiographic changes in uncomplicated falciparum malaria patients.

Asymptomatic sinus bradycardia and sinus arrhythmia have been noted in malarial patients receiving mefloquine. The present study was designed to assess the effect of mefloquine on electrocardiogram in malarial patients. The study was carried out in 102 acute uncomplicated falciparum malarial patients who were treated with mefloquine 750 mg and 1,250 mg regimens and 18 healthy male volunteers receiving 750 mg of mefloquine. Electrocardiogram was performed at intervals after mefloquine administration for a period of 42 days. PR, QRS, QT, QTc, RR interval and cardiac arrhythmia were measured and read by EKG-analyser with confirmation by a cardiologist. Sinus bradycardia and sinus arrhythmia were found in 61.8% and 45.1%, respectively during the first week after treatment. The patients' heart rate decreased significantly on day 6 after mefloquine administration when compared to day 0. The occurrence of sinus bradycardia and sinus arrhythmia were significantly higher in malarial patients when compared with findings in healthy subjects of the same age group. It is unlikely that these changes are associated with mefloquine concentration as mefloquine peaks around 12-24 hours after administration. There were no significant changes in PR-interval, QRS-interval and QTc interval on the electrocardiogram. The findings in this study suggest that cardiotoxicity from mefloquine is unlikely. Bradycardia may be the result of autonomic control modulation after resolution of high fever.

Adolescent↗