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Biomedical subjects

J Karbwang

Publications and source records attributed to J Karbwang.

At least 127 records · Page 7Linked to original sources
PubMed1988

Inhibition of tolbutamide metabolism by antimalarial drugs.

The effects of mefloquine (MQ), the combination of MQ with sulfadoxine-pyrimethamine (MSP), sulfadoxine (S), pyrimethamine (P) quinine (Q) and quinidine (Qd) on in vitro hepatic metabolism has been studied using tolbutamide as a substrate. The hydroxylation of tolbutamide was determined in the presence of variable concentrations of each compound. Tolbutamide hydroxylase activity in control microsomes was 0.20 +/- 0.13 nmole/min/mg microsomal protein at a substrate concentration of 150 microM. All compounds studied inhibited tolbutamide metabolism as shown by a decrease in 4-hydroxytolbutamide formation. The order of potency of the inhibitors was MSP greater than S greater than MQ greater than Q greater than Qd greater than P. MQ, MSP, S, Q, and Qd were examined in detail for the type of inhibition. MQ and Qd were non-competitive inhibitors, whereas MSP and S were competitive inhibitors and Q was an uncompetitive inhibitor of tolbutamide 4-hydroxylation. These data provide more information on the inhibitory potential of some antimalarial drugs on microsomal enzymes in human liver. S has been shown to be a potent inhibitor in vitro and this finding possibly explains the longer T 1/2 and MRT of MQ when co-administered with S in healthy volunteers. Further studies in man should be attempted in order to understand the clinical relevance of the inhibitory potential of the antimalarial drugs.

Adult↗
PubMed1987

The pharmacokinetics of mefloquine when given alone or in combination with sulphadoxine and pyrimethamine in Thai male and female subjects.

The kinetics of mefloquine were studied in 12 healthy Thai male and 12 healthy Thai female volunteers. Mefloquine (MQ) was administered either alone (750 mg orally) or in combination (MSP) with sulphadoxine (1.5 g) and pyrimethamine (75 mg) to each of 6 male and 6 female subjects. Plasma concentrations of MQ were measured by HPLC at intervals for 42 days. There was considerable interindividual variability in the pharmacokinetic parameters; for example in the male subjects receiving MQ alone peak concentrations ranged between 638 and 2494 ng X ml-1 with a mean concentration of 1442 ng X ml-1. Compared to previously published data on MQ concentrations in Caucasian male subjects, the present study indicates that higher concentrations are achieved in Thai subjects. The only significant difference in kinetic parameters between male and female subjects receiving MQ alone was in the mean residence time (MRT) which was greater in females. However, an analysis of pharmacokinetic parameters following administration of the combination preparation showed that the time to peak (tmax) was significantly reduced in females receiving MSP compared to the corresponding females given MQ alone and males given MSP. When data obtained from all subjects (male and female) receiving either MQ alone or MSP were combined, both MRT and half-life were significantly greater in subjects given MSP. There is therefore some evidence that therapeutic concentrations of MQ are maintained for a longer period of time following MSP administration.

Adult↗
PubMed1987

Antibody response to suckling mouse brain rabies vaccines for post exposure treatment.

A new suckling mouse brain vaccine (SMBV) against rabies, produced by the Thai Red Cross Society, was compared with the well established Institut Pasteur SMBV in patients with very low risk rabies contact. The 4 regimens used were the standard daily injections with booster doses of Thai Red Cross vaccine (TRCV) and Institut Pasteur Vaccine (IPV), and a reduced dose scheme of 6 injections as used for tissue culture vaccines. The effect of 20 IU/kg of human rabies immune globulin (HRIG) was tested on each regimen, making 8 groups, a total of 122 patients. Blood samples taken on days 0, 7, 14, 28 and 91 were tested for neutralizing antibody. Only the standard IPV regimen produced antibody in every patient; all had levels greater than 0.5 IU at some stage. Two people (13%) given the standard TRCV produced no detectable antibody (less than or equal to 0.1 IU) throughout the study. The reduced dose regimens gave very low antibody levels. 7% of the IPV and 76% of the TRCV groups failed to produce antibody on any occasion. The antibody response was significantly suppressed by the administration of HRIG. Compared to the original South American SMBV, the vaccines tested induced low levels of short lived antibody. No reduction in the dosage of SMBV should be considered unless the potency of the product is adequate.

Adult↗
PubMed1987

Plasma concentrations and toxicity of chloroquine after slow intravenous infusion in patients with falciparum malaria.

Five male patients with acute Plasmodium falciparum or Plasmodium vivax infections were infused with chloroquine diphosphate (15 mg kg-1) over four hours. Further does of chloroquine diphosphate (5 mg kg-1) were given at 12, 24, 36 and 60 hours. Plasma chloroquine concentrations were determined before and four hours after each dose and then daily until discharge. No serious cardiovascular toxicity was observed, and plasma chloroquine concentrations exceeding the putative minimum inhibitory concentration (MIC) of sensitive P. falciparum strains were reached within four hours of starting treatment. Further doses produced plasma concentrations which were sustained above the putative MIC, but showed no rapid increase into the range associated with toxicity.

Adolescent↗
PubMed1987

Pharmacokinetics of intravenous amodiaquine.

Amodiaquine hydrochloride (3 mg base kg-1) was given by constant rate intravenous injection over 10 min to seven healthy adult male volunteers, and by constant rate infusion (10 mg base kg-1) over 4 h to 10 adult patients admitted to hospital with falciparum malaria. After intravenous injection in volunteers there was considerable variation in plasma concentration profiles between subjects; peak plasma concentrations ranged between 65 and 1921 ng ml-1. A biexponential equation was fitted to the plasma concentration time data and the following estimated pharmacokinetic parameters (geometric mean; range) were derived; lambda 1 = 24.4 (7.6-95.0) h-1, lambda 2 = 0.33 (0.12-0.79) h-1, V1:1.1 (0.3-3.6) 1 kg-1, Vss: 17.4 (2.3-95.9) 1 kg-1 and systemic clearance 13.0 (4.7-56.6) 1 kg-1 h-1. After intravenous infusion there was also considerable variability between patients with post-infusion plasma concentrations ranging between 82 and 836 ng ml-1. The plasma concentration-time profiles were biphasic with the following estimated pharmacokinetic parameters (geometric mean; range) alpha = 1.87 (0.60-8.52) h-1, beta = 0.069 (0.021-0.265) h-1, V1: 4.6 (0.5-29.3) 1 kg-1, Vss: 38.3 (3.7-127.9) 1 kg-1 and systemic clearance CL (1.6-17.3) 1 kg-1 h-1. There was no measurable long terminal elimination phase, and the principal metabolite desethyl amodiaquine was not detected in the plasma samples. There was no serious toxicity in either group. During intravenous injection there was a significant fall in systolic blood pressure in four subjects (mean fall 16 mm Hg) but there was no significant change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Plasma and whole blood mefloquine concentrations during treatment of chloroquine-resistant falciparum malaria with the combination mefloquine-sulphadoxine-pyrimethamine.

Mefloquine-sulphadoxine-pyrimethamine (MSP) in combination has proved effective against multiple-drug-resistant falciparum malaria, but nothing is known about mefloquine absorption when it is given in this formulation. Nine Thai patients, aged 15-51 years with uncomplicated chloroquine-resistant falciparum malaria, took 11.2-16.7 mg of mefloquine base per kilogram bodyweight as MSP tablets. All patients responded to treatment with fever and parasite clearance times of 61 +/- 29 h (mean +/- s.d.) and 52 +/- 24 h, respectively. The mean apparent absorption half-time (t1/2abs) of mefloquine was 4.89 h (range 2.25-9.72) and mean peak plasma concentration was 1815 ng ml-1 (range 725-3368). Peak plasma mefloquine concentrations in three patients who vomited within 2 h of treatment were 725, 956 and 1972 ng ml-1. There was no significant difference between plasma and whole blood mefloquine concentrations during the first 48 h of treatment. Based on the elimination of parasitaemia, the plasma mefloquine concentrations are adequate for therapy of uncomplicated falciparum malaria although the relationship between plasma concentrations and therapeutic efficacy of mefloquine requires further study.

Adolescent↗
PubMed1986

Hypoglycaemia and antimalarial drugs: quinidine and release of insulin.

Life threatening hypoglycaemia has been closely associated with the use of quinine, but the effect of quinidine and the synthetic antimalarials on the homoeostasis of glucose has not been investigated. In volunteers given a fixed dose of 500 mg base and patients with malaria given a quinidine loading dose (15 mg base/kg) mean (SEM) plasma insulin concentrations rose from 6.1 (1.5) mU/l to 10.9 (4.4) mU/l (p less than 0.02) and 10.4 (2.0) mU/l to 18.5 (5.3) mU/l (p less than 0.04), respectively. Plasma glucose concentrations fell from 4.5 (1.1) mmol/l (81 (20) mg/100 ml) to 4.0 (0.3) mmol/l (72 (5) mg/100 ml) in volunteers (p less than 0.04) and from 5.7 (1.3) mmol/l (102 (23) mg/100 ml) to 4.8 (1.6) mmol/l (86 (29) mg/100 ml) in patients (p less than 0.05). One of two patients with cerebral malaria and acute renal failure became profoundly hypoglycaemic (plasma glucose concentration 1.4 mmol/l (25 mg/100 ml), plasma insulin concentration 3.1 mU/l). Hypoglycaemia may occur in any severely ill fasting patient given parenteral quinidine. The other antimalarials tested, chloroquine, amodiaquine, mefloquine, and halofantrine, did not stimulate the release of insulin, an important advantage that should be taken into account when treatment is chosen for Plasmodium falciparum malaria.

Amodiaquine↗
PubMed1986

Purified Vero cell rabies vaccine and human diploid cell strain vaccine: comparison of neutralizing antibody responses to post-exposure regimens.

Neutralizing antibody responses to conventional rabies post-exposure regimens of human diploid cell strain vaccine (HDCSV) and the new purified Vero cell rabies vaccine (PVRV) were compared in 58 healthy Thai veterinary students. The geometric mean titres (GMTs) of the group given HDCSV were slightly higher than those given PVRV, but on day 28 the peak GMTs of the two groups were statistically similar. The early antibody response to PVRV was unaffected by the addition of passive immunization, whereas the level of HDCSV response was reduced on day 14, so that there was no difference on that day between the GMTs of the two vaccine groups given HRIG. However, by day 91 the GMT of those given PVRV and HRIG was lower than in those given HDCSV alone or with HRIG. The appearance of antibody was less rapid than was observed in previous studies using multiple-site intradermal vaccination. Side effects were trivial. Our results confirm the promise of this new, potentially more economical tissue culture vaccine, but they suggest that the regimen could be improved.

Adolescent↗
PubMed1986

Randomized comparative trial of three monospecific antivenoms for bites by the Malayan pit viper (Calloselasma rhodostoma) in southern Thailand: clinical and laboratory correlations.

Three monospecific antivenoms for Malayan pit viper (MPV) (Calloselasma rhodostoma) were compared in Southern Thailand, where this species is the most common cause of snake bite morbidity. Forty-six patients with proved MPV bites and incoagulable blood, indicating systemic envenoming, were randomly allocated for treatment with Thai Red Cross (TRC), Thai Government Pharmaceutical Organization (GPO), or Twyford Pharmaceutical monospecific antivenoms. Both GPO and Twyford antivenoms produced rapid and permanent restoration of blood coagulability, but TRC antivenom failed in 2/15 cases. Patients in the GPO group showed the greatest increase in plasma fibrinogen concentration during the first 24 hr and had fewer early anaphylactic reactions (6/15) compared with Twyford 8/16 and with TRC 13/15. Pyrogenic reactions occurred more frequently after TRC antivenom (8/15) than GPO (1/15) or Twyford (0/16). Patients requiring more than one dose of antivenom were identifiably more severely envenomed on admission. In an accompanying laboratory study the antivenoms were assessed in rodents using five WHO standard tests of neutralizing activity. Compared with the other two antivenoms TRC was significantly inferior in anti-lethal potency, GPO was superior in anti-hemorrhagic and anti-necrotic potency and Twyford was superior in anti-procoagulant and anti-defibrinogenating potency. The clinical efficacy of these antivenoms against local necrosis remains equivocal. GPO and Twyford antivenoms are recommended for the treatment of systemic envenoming by MPV in an initial dose of 5 ampoules.

Adult↗
PubMed1986

Clinical significance of venom antigen levels in patients envenomed by the Malayan pit viper (Calloselasma rhodostoma).

Serial venom antigen levels were measured by enzyme-linked immunosorbent assay (ELISA) in 46 patients with systemic envenoming by the Malayan pit viper (Calloselasma rhodostoma), a major cause of snake bite in Southeast Asia. The principal effects of the venom are defibrination, hemorrhage and local tissue necrosis. Admission venom levels, which varied between 0 and 595 ng/ml, correlated with the incidence of spontaneous systemic bleeding, blood incoagulability and concentrations of plasma fibrinogen and serum fibrin degradation products. The presence or absence of nonclotting blood also correlated with the time elapsed between the bite and hospital admission. The development of nonclotting blood may be delayed by up to 72 hr after the bite even though circulating venom and raised FDP may be detected at presentation. This is probably explained by a temporary equilibrium between synthesis and consumption of fibrinogen. Venom antigenemia recurred in 12 patients (26%) suggesting continuous absorption of venom from the wound or saturation of extravascular binding sites. Admission venom levels also correlated with the extent of local swelling and the occurrence of tissue necrosis at the site of the bite. Venom was detected in 87% of wound aspirates and 88% of urine specimens taken on admission. Tourniquets, of the type used in rural Thailand, did not delay the absorption of venom into the circulation.

Adolescent↗
PubMed1986

The importance of anaemia in cerebral and uncomplicated falciparum malaria: role of complications, dyserythropoiesis and iron sequestration.

Ninety-four per cent of 169 patients with cerebral malaria developed anaemia (haematocrit less than 35 per cent) and 30 per cent required blood transfusion to maintain the haematocrit at more than 21 per cent. Anaemia was at its worst on admission in 58 patients (34 per cent); in the rest the haematocrit fell further, reaching its nadir one to 17 days later (mean 2.3 days). The mean lowest haematocrit was 24.3 +/- 7.2 per cent (+/- 1 SD) and the mean maximum fall was 7.9 +/- 5.6 per cent. Anaemia was more severe in patients with bacterial infection, retinal haemorrhages, schizontaemia and in pregnancy. The lowest haematocrit correlated with admission parasitaemia (r = -0.33, p less than 0.001), total serum bilirubin (r = -0.25, p less than 0.01) and serum creatinine (r = -0.22, p less than 0.01). In 23 patients with uncomplicated falciparum malaria the mean serum iron on admission was 53 micrograms/dl (range 16-157) and the mean serum ferritin 1773 ng/ml (range 170-10 000). There was a significant (p less than 0.001) rise in serum iron 96 h after starting antimalarial treatment; the serum ferritin declined slowly over several weeks. Stainable iron was present in all marrows examined and in eight patients the characteristic pattern of the anaemia of chronic disorders was seen. Seventy-three per cent of patients had dyserythropoiesis which was moderate to gross in 36 per cent. Dyserythropoiesis and erythrophagocytosis were often present on admission but sometimes appeared after the parasitaemia had cleared and persisted for at least three weeks into convalescence. These disturbances in iron metabolism and haemopoiesis are not completely explicable by red blood cell parasitisation. They may contribute more to the anaemia than has previously been recognised.

Adolescent↗
PubMed1985

Intravenous amodiaquine and oral amodiaquine/erythromycin in the treatment of chloroquine-resistant falciparum malaria.

In eastern Thailand, 14 adults with moderately severe falciparum malaria were treated with intravenous amodiaquine dihydrochloride, loading dose 10 mg base/kg infused over 4 h followed by three further intravenous infusions of 5 mg base/kg at 24, 48, and 72 h. All patients were clinically cured--mean fever clearance time 37.8 h (range 24-60), mean parasite clearance time 64.9 h (18-164). There were no serious toxic effects. 33 patients aged over 5 years with uncomplicated falciparum malaria were given oral amodiaquine dihydrochloride (mean total dose 41 mg base/kg over 3 days) combined with erythromycin estolate (mean dose 48 mg base/kg daily for 5 days). 2 patients failed to respond. In the other 31 patients mean fever clearance time was 55.9 h (range 10-104) and mean parasite clearance time was 65.4 h (40-120). In both studies, more than half the patients followed-up had recurrent parasitaemia but reinfection could not be excluded. Parasites isolated from 18 patients were highly resistant to chloroquine in vitro.

Administration, Oral↗
PubMed1985

Quinine and severe falciparum malaria in late pregnancy.

Quinine dihydrochloride was given intravenously to 12 women with severe falciparum malaria in the third trimester of pregnancy. The initial dose consisted of 10 or 20 mg salt/kg over 4 h and was followed by 10 mg salt/kg every 8 h until patients were fit to swallow, when quinine sulphate tablets were given. Uterine activity showed little or no change despite rising quinine concentrations. Of 3 patients in labour, 2 proceeded normally while a third had a successful caesarean section for fetal distress. Late (type II) decelerations of the fetal heart rate were recorded in 6 patients before treatment but in most patients signs of fetal distress diminished as the maternal temperature fell. Hypoglycaemia and hyperinsulinaemia developed in 7 patients, in 2 before quinine was started. The important toxic effect of quinine in late pregnancy is not an oxytocic action but rather its capacity to release insulin.

Adolescent↗
PubMed1985

Intravenous quinidine for the treatment of severe falciparum malaria. Clinical and pharmacokinetic studies.

Quinidine has proved more effective than quinine against chloroquine-resistant Plasmodium falciparum both in vitro and in patients with uncomplicated disease. To examine the effectiveness and pharmacokinetics of quinidine for this use, we treated 14 patients who had severe falciparum malaria with intravenous quinidine gluconate; a loading dose of 15 mg of the base per kilogram of body weight was followed by 7.5 mg per kilogram every eight hours. Two of the five patients with cerebral malaria died, but parasitemia was eliminated in the 12 survivors. Two patients had recurrent parasitemia on Days 25 and 28. Times required for parasite clearance and elimination of fever (49.4 +/- 17.8 and 69.5 +/- 18.7 hours, respectively) were comparable to those in earlier studies with a loading dose of quinine. Quinidine appears to have a larger volume of distribution than quinine. The elimination half-life was 12.8 hours, the volume of distribution was 1.68 liters per kilogram, total clearance was 1.75 ml per kilogram per minute, and urinary clearance was 0.62 ml per kilogram per minute. Electrocardiographic changes were common but there were no dysrhythmias. In two patients, blood pressure fell during the initial infusion of quinidine. Quinidine gluconate is more widely available than quinine in many countries, and our findings show that it is effective in severe falciparum malaria.

Adolescent↗
PubMed1985

Lack of interferon induction in man by two rabies tissue culture vaccines.

Both neutralising antibody and interferon play a part in protection of animals against death from rabies virus infection. Interferon induction was therefore sought in 53 volunteers within 24 hours of receiving human diploid cell strain vaccine or fetal bovine kidney cell vaccine given either intramuscularly or intradermally. Repeat observations were made in 18 subjects following a second dose of vaccine seven days later. No interferon was detected in any sample tested although no subject had any detectable rabies neutralising antibody on day 0. The sensitivity of the interferon assay, and comparison with other studies are discussed. An interferon inducer suitable for human use should be sought as an alternative to, or a replacement for, passive rabies immunization.

Adolescent↗
PubMed1984

Failure of chloroquine-erythromycin and chloroquine-tetracycline combinations in treatment of chloroquine-resistant falciparum malaria in eastern Thailand.

In Eastern Thailand the increasing resistance of Plasmodium falciparum to all available antimalarial drugs prompted a reassessment of chloroquine in combination with either erythromycin or tetracycline. Both combinations had produced encouraging results in vitro, in experimental animal models, or in preliminary clinical trials. In patients with uncomplicated falciparum malaria presenting with moderate parasitaemia the trial of chloroquine and tetracycline was abandoned after RIII resistance with clinical deterioration was encountered in 2 out of the first 5 patients studied. Of 16 patients treated with chloroquine+erythromycin, 11 showed resistance (RI-RIII). These regimens appear ineffective and potentially dangerous in Eastern Thailand.

Adolescent↗
PubMedDate not supplied

Absence of significant pharmacokinetic and pharmacodynamic interactions between artemether and quinoline antimalarials.

The study was carried out to investigate the pharmacokinetic and pharmacodynamic interactions between artemether (ARTEM) and quinoline antimalarials namely mefloquine (MQ), quinine (QN) and primaquine (PQ) when given concurrently. A randomised comparative, seven way cross-over design was performed in eight healthy male Thais following the administrations of seven drug regimens on seven occasions i.e. a single oral dose of ARTEM (300 mg), or MQ (750 mg), or QN (600 mg), or PQ (45 mg) alone, or the combination of ARTEM (300 mg) with MQ (750 mg), or QN (600 mg), or PQ (45 mg). All clinical and laboratory parameters were normal in all subjects, before, during and after the study. The eight subject experienced no adverse effect after ARTEM, QN, PQ alone regimens, or combination of ARTEM with QN and PQ. After administration of MQ in either occasion, 3 subjects had weakness, nausea, abdominal pain, and diarrhoea; one subject complained of dizziness. All symptoms were mild and occurred during the first day of MQ administration. The fitting of the concentration-time curves of ARTEM, QN and PQ, to a one-compartment model with first order absorption yielded satisfactory results in all subjects. The best fit model for MQ was two-compartment model with first order absorption. The pharmacokinetics of all investigated drug, when given alone or in combination were not significantly different.

Adult↗