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Biomedical subjects

U Hellgren

Publications and source records attributed to U Hellgren.

At least 37 records · Page 2Linked to original sources
PubMed1994

High-performance liquid chromatographic method for the enantioselective analysis of mefloquine in plasma and urine.

An HPLC method for analysis of the enantiomers of the antimalarial drug mefloquine is presented. A complete resolution of (-)-(11S,2'R) and (+)-(11R,2'S) erythro-mefloquine from plasma and urine was obtained on a commercial AGP column. Mefloquine enantiomers were detected by UV at 222 nm. The separation factor (alpha) at +20 degrees C was 1.50. The limit of determination (coefficient of variation 4.0%) for the enantiomeric ratio (11S,2'R)/(11R,2'S) is 15:1 at a total mefloquine concentration of 1.6 mM.

Chromatography, High Pressure Liquid↗
PubMed1994

Malaria parasites and chloroquine concentrations in Tanzanian schoolchildren.

Subtherapeutic doses of chloroquine (CQ) are considered to promote development of Plasmodium falciparum resistance but little is actually known about the drug levels in the population in endemic areas. We have therefore measured blood concentrations of CQ in Tanzanian schoolchildren and related these to parasite microscopy. A total of 163 children (median age 11 years) in a suburb outside Dar es Salaam were followed during four weeks. Thick and thin blood films were obtained once weekly. Parasites were counted in 200 visual fields. CQ and desethyl-chloroquine (DECQ) were determined with HPLC in 100 microliters of capillary blood. During the study P. falciparum trophozoites were detected in a mean of 78% of the children, P. falciparum gametocytes in 7.7% and P. malariae parasites in a mean of 13%. The cumulative prevalence of P. falciparum trophozoites and P. malariae parasites was 96% and 28% respectively. On day 0 and day 28, CQ was found in 78% and 80% of the children and DECQ in 21% and 31% of them. A total of 19% of all children had a verified CQ intake during the study and 35% had probably taken CQ. With a few exceptions (9% had CQ concentrations > 100 nmol/l) drug levels were not sufficient to affect parasites with a reduced CQ susceptibility but could possibly promote development of resistance by eradicating the most susceptibility part of the parasite population.

Adolescent↗
PubMed1994

Falciparum malaria in eastern Thailand: a randomized trial of the efficacy of a single dose of mefloquine.

Reported are the results of a randomized trial of a single dose of mefloquine (15 mg/kg or 25 mg/kg body weight) for the treatment of uncomplicated multidrug-resistant falciparum malaria. Of the 110 adult patients enrolled in the study 57 were randomly assigned to the 15 mg/kg group and 53 to the 25 mg/kg group. The baseline characteristics of the patients did not differ significantly in the two groups, except that those in the 15 mg/kg group had lower haemoglobin levels. Adverse effects following treatment were commoner in the 25 mg/kg group, but not significantly so. Seven patients (6%) did not complete the 42-day follow-up. The parasitological failure rates in the 15 and 25 mg/kg groups were, respectively, 50% (28/56) and 43% (25/53) on day 28, and 62% (33/53) and 56% (28/50) on day 42. Treatment failures were not correlated with the serum mefloquine concentrations on day 2, and 13 out of 19 patients with serum mefloquine concentrations > 2000 micrograms/l on day 2 showed an R response during the follow-up. The mean ratio between the concentrations of the (SR)-(-) and (RS)-(+) enantiomers of mefloquine on day 2 was 3.37, indicating that there are differences in their pharmacokinetics. Re-treatment of patients who showed an R response with seven days of quinine (30 mg.kg-1.day-1)+tetracycline (25 mg.kg-1.day-1) was successful in 93% of the cases.

Adult↗
PubMed1993

On the question of interindividual variations in chloroquine concentrations.

In a review of studies using appropriate methods for drug determinations and controlled intake, an interindividual variation in chloroquine concentrations of 2.3 to 5.6-fold was found. In our department, steady-state concentrations were evaluated in 40 patients with rheumatic diseases. The variation in whole blood concentrations was 11-fold for chloroquine and 10-fold for the desethylchloroquine metabolite. The mean ratio between desethylchloroquine and chloroquine concentrations was 0.53 and the Spearman-Rank correlation 0.92. The correlation between age and the ratio of chloroquine concentration/dose was 0.36 (P < 0.05) and the corresponding correlation for body weight was -0.43 (P < 0.05). Our data indicate that body weight and age are important independent factors for the disposition of chloroquine. However, when extensive 100-fold variations in concentrations are found between individuals we suggest that the reliability of the dose intake should be questioned.

Adult↗
PubMed1993

Lack of effect of amoxycillin on the absorption of ofloxacin.

Amoxycillin and ofloxacin are both well absorbed after oral administration, despite being hydrophilic. We have studied the possibility of competition between these two drugs for a carrier-mediated transport system, since both drugs are absorbed by saturable processes in the rat small intestine. Oral doses of amoxycillin (3 g) and ofloxacin (400 mg) were given separately and in combination to six healthy volunteers. Blood samples were taken over 30 h and plasma concentrations of the respective drugs were measured by HPLC. Amoxycillin did not alter the pharmacokinetics of ofloxacin.

Adult↗
PubMed1993

Reversed-phase high-performance liquid chromatography determination of quinine in plasma, whole blood, urine, and samples dried on filter paper.

The analysis of quinine in whole blood, plasma, urine, and samples dried on filter paper is described. Extraction was made with toluene followed by back-extraction into phosphate buffer. A reversed-phase liquid chromatography system with fluorescence detection was used. The within-day coefficient of variation of the method was 4-10% at the lower limit of determination (2 nM in plasma and 50 nM in whole blood, dried samples, and urine) and 2-4% at 10 microM. The quinine concentration was found to be lower in whole blood than in plasma (mean ratio, plasma-whole blood, 1.17). The concentration in capillary blood was lower than that in venous blood (mean ratio, capillary blood-venous blood, 0.93).

Capillaries↗
PubMed1993

Comparative tolerability and kinetics during long-term intake of Lariam and Fansidar for malaria prophylaxis in nonimmune volunteers.

One hundred and five healthy nonimmunes in Colombia took part in a randomize, double-blind comparison of 250 mg of Lariam (L) (active ingredient: mefloquine) on alternate weeks or one tablet of Fansidar (F) (active ingredients: sulfadoxine and pyrimethamine) weekly for malaria prophylaxis during at least six months. Volunteers also gave blood for determination of drug concentrations after six months and/or 24-27 months of prophylaxis. Twenty-five volunteers withdrew involuntarily when they lost their jobs in the company. Two who took L withdrew due to moderate diarrhea and mild nausea or headache, weakness, drowsiness and anxiety. One volunteer stopped taking F due to severe unilateral hypostatic eczema and slight S-T depressions on the ECG. The rest completed at least six (range 6-36) months of prophylaxis. The mean half-life for L was 26 days. The AUCs in the time interval 0-14 days for L varied between 19.3-31.5 mumol x days/l. For the main metabolite, the corresponding range was 28.8-81.3 mumol x days/l. The range of trough concentrations at day 0 and 14 were 0.95-2.01 mumol/l for L and 1.69-5.62 mumol/l for the metabolite. No differences in tolerability and efficacy were noted between L and F. Our kinetic results do not indicate that enzymatic induction or inhibition would be important during long-term prophylaxis with mefloquine. This favors a continued use of the drug for very long periods of time (= years).

Adult↗
PubMed1993

[Mefloquine and sulfadoxine/pyrimethamine overdose in malaria tropica].

A 39 year-old man with malaria due to Plasmodium falciparum received 3500 mg mefloquine over 3 days, in addition to 3250 mg chloroquine and 175/3500 mg sulfadoxine/pyrimethamine. He developed severe neuropsychiatric symptoms and had to be hospitalized. Treatment with diazepam, haloperidol and thioridazine achieved relief of the severe symptoms after 4 days. The patient was still suffering from discrete neuropsychiatric symptoms 8 months after treatment.

Adult↗
PubMed1991

Hearing impairment related to plasma quinine concentration in healthy volunteers.

1. Hearing impairment was investigated in six healthy volunteers who received oral doses of 5, 10 and 15 mg kg-1 quinine single-blind and in random order. 2. The plasma concentration of quinine was followed for 48 h and the time course was fitted by a linear one compartment pharmacokinetic model. 3. Hearing thresholds were measured by pure tone audiometry. There was a delay between impairment in hearing and change in plasma quinine concentration. Thus the method of effect compartment modelling was applied. 4. The effect on hearing (L), measured as a shift in hearing threshold (dB), was used to estimate the rate constant for elimination of drug from the assumed effect compartment (ke0) and two parameters specifying the effect model (gamma and k). The effect model applied was L = 10 (log k + gamma x log Ce) where Ce is the calculated drug concentration in the effect compartment. This model is a logarithmic transform of a power expression equivalent to the Hill equation at the lower end of the effect range. In all experiments where there was a clear effect on hearing, convergence on a set of parameter estimates occurred, but inter- and intraindividual variability was large. The mean value of ke0 was 3.32 +/- 5.93 h-1 s.d., for gamma it was 1.73 +/- 1.14 s.d. and for k it was 0.59 +/- 0.66 s.d.

Adult↗
PubMed1991

Standard and reduced doses of mefloquine for treatment of Plasmodium falciparum in Tanzania: whole blood concentrations in relation to adverse reactions, in vivo response, and in vitro susceptibility.

Fifty-three asymptomatic Tanzanian school children with 400-31,000 asexual Plasmodium falciparum parasites/microliter of blood were given standard, one-half, one-quarter, or one-eighth of the recommended mefloquine treatment dose of 25 mg base/kg body weight. Mefloquine and main metabolite concentrations were determined in 100 microliters of capillary blood using a high performance liquid chromatographic method. In the standard, one-half, and one-quarter dose groups, all children cleared the parasites within three days after treatment. Reappearance was noted in one of the children in the one-quarter dose group during 49-56 days of followup. Among the children given one-eighth of a dose, two had an RII response and four had an RI response with early recrudescence. All 24-hour in vitro micro-tests (n = 30) showed full susceptibility for mefloquine. Adverse gastrointestinal reactions were reported by eight children on the first day after treatment, four of whom had been given a standard dose. These children had higher mefloquine concentrations one day after treatment than the other children in this group (P less than 0.05). In the standard dose group (n = 13), the area under the curve of capillary whole blood concentrations of mefloquine versus time was 52.4-112.1 mumol/liter x days. The highest concentration on day 1 was 2.75-7.20 mumol/liter and the median terminal half-life was 17.4 days. The highest concentrations of the main metabolite were observed 1-2 weeks after treatment and the median half-life was 18.9 days. The concentrations in the other groups were approximately proportional to those in the standard dose group both for mefloquine and the metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Clearance of plasmodium falciparum after reduced single daily doses of quinine in asymptomatic children in Guinea Bissau.

Asymptomatic schoolchildren in Guinea Bissau were given approximately 10 mg of quinine/kg body weight once daily during 5 days (n = 15) or 3 days (n = 16) for treatment of P. falciparum. Five children had parasitemia on the seventh day of follow up. Adverse reactions were reported by 12 children during treatment, mainly mild tinnitus, dizziness and vomiting. Single daily doses were less effective than the divided doses previously used by us for the same short time period and also associated with more frequent adverse events.

Adolescent↗
PubMed1991

Low doses of quinine during a short time period are effective for clearance of Plasmodium falciparum in asymptomatic children in Guinea Bissau.

Asymptomatic children in Guinea Bissau were given 5 mg quinine per kg body weight two times daily for 5 days (n = 18) or 3 days (n = 20) for treatment of Plasmodium falciparum. Parasites disappeared within four days after initiation of treatment and remained absent during the first week afterwards. Six children reported adverse reactions, mainly mild tinnitus which disappeared after termination of treatment. Reduced doses of quinine for shorter treatment periods was effective in this study. Further studies in symptomatic patients are needed to elucidate whether this low-dose regimen could be an alternative to chloro-quine in the treatment of P. falciparum in Africa.

Adolescent↗
PubMed1989

Local anaesthetic cream for the alleviation of pain during venepuncture in Tanzanian schoolchildren.

The analgesic effect and the usefulness of EMLA cream 5% in connection with venous blood-sampling was investigated in 42 Tanzanian schoolchildren. Approximately 2.5 g EMLA was applied to the right cubital fossa for a minimum of 120 min. The analgesic effect was pronounced--93% of the venepunctures were pain-free and no child experienced severe pain. No adverse reactions were observed and the children could continue normal school work during the application time.

Adolescent↗