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Biomedical subjects

L Rombo

Publications and source records attributed to L Rombo.

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

Plasma pentamidine concentrations vary between individuals with Pneumocystis carinii pneumonia and the drug is actively secreted by the kidney.

The multiple-dose pharmacokinetics of pentamidine were studied in six AIDS patients with acute Pneumocystis carinii pneumonia given infusions of pentamidine isethionate 3.7-4 mg/kg/day i.v. Plasma and urine concentrations of pentamidine of repeated samples taken on days 1, 4 and 7 of treatment were assayed by HPLC. Creatinine clearance Clcr was also determined. On day 7, the area under the plasma concentration versus time curve (AUC) varied fourfold (3263 to 12776 nmol.h/L) between individuals. It was lowest in a patient receiving concomitant treatment with carbamazepine, suggesting that this drug may induce the metabolism of pentamidine. On day 7, a mean of 12% of the dose was excreted unchanged in the urine. Clcr was decreased significantly on day 7 compared with day 1 (mean decrease 31%, range 11-63%). Renal clearance of pentamidine (Clr) decreased over time but always exceeded the Clcr, indicating tubular secretion. The decrease of Clr may be explained by capacity-limited secretion and/or a tubulotoxic effect of the drug. The variation of the AUC values is consistent with interindividual differences in rates of metabolism, which supports individual dosing strategies for pentamidine.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Pentamidine accumulates in rat liver lysosomes and inhibits phospholipid degradation.

The subcellular distribution and the effects of pentamidine on the ultrastructure of the rat liver were studied. Rats were given single or repeated daily intraperitoneal injections of 10, 25 or 50 mg pentamidine isethionate/kg b. wt. for 1, 4, 6, 9 or 16 days. The livers were removed for ultrastructural and biochemical analyses on the day after termination of each series of injections and in addition 7 and 35 days after the 16th injection. Electron microscopy of liver tissues showed that the general cellular architecture of the hepatocytes was preserved. The subcellular organelles were normal, except for the secondary lysosomes, which were severely altered and laden with multilamellar, myelin structures (myelin bodies) that gradually increased with dose and time course following repeated injections. These altered lysosomes were enriched in phospholipids. The alteration of the lysosomes persisted for up to 5 weeks after cessation of administration. Pentamidine was highly enriched in the lysosomal fraction (30-50 times more than in the liver homogenate). It was calculated that the lysosomal pentamidine accounted for practically all pentamidine distributed to the liver. The demonstrated accumulation of pentamidine in the lysosomes may explain the known large volume of distribution of this drug and may be one mechanism for organ toxicity.

Animals↗
PubMed1994

Intestinal parasites in refugees and asylum seekers entering the Stockholm area, 1987-88: evaluation of routine stool screening.

In order to evaluate the results of routine screening for intestinal parasites, the medical records of 4592 refugees and asylum seekers arriving in the Stockholm area from January 1987 to December 1988 were reviewed. 3938/4592 (86%) delivered stool specimens for examination and intestinal parasites were demonstrated in 651/3938 (17%). Protozoa, mainly Giardia intestinalis, were found in 403/3938 (10%) and helminths, mainly nematodes, in 277/3938 (7%). Intestinal parasites were most frequently recovered in subjects coming from the Indian subcontinent/Southeast Asia and Africa (infection rates 39% and 25%, respectively). Extensive variations in the prevalence of intestinal parasite infection in various ethnic groups (range 4%-39%) were largely attributable to variations in prevalence of helminthic infections (range 2%-34%). Origin from the tropics or subtropics as well as low age, male sex, rural region of domicile before/during exile and short length of stay in Sweden were related to intestinal parasitic infection. Lack of data on morbidity in untreated asymptomatic carriers, limited risks for transmission of the recovered parasites in Sweden as well as the expenses for screening indicate a need for reconsideration of the present praxis of mass screening in favour of a selective screening of high-risk groups based on country of origin and age.

Adolescent↗
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↗
PubMed1993

High-performance liquid chromatographic method for the simultaneous determination of mefloquine and its carboxylic metabolite in 100-microliters capillary blood samples dried on paper.

A reversed-phase high-performance liquid chromatographic method is described for the analysis of mefloquine and its carboxylic metabolite in 100-microliters capillary blood spots dried on chromatographic paper. Each spot was cut into small pieces, and mefloquine and its metabolite were eluted with an ammonia-water solution (10:90, v/v). The compounds were extracted simultaneously after alkalization at pH 9.5 using tetrabutylammonium as ion-pairing agent and then separated on a C18 column with ultraviolet detection at 227 nm. The recovery of the drugs from spiked blood applied to paper and dried was 70-80%, and the inter-assay precision at 1.0-5.0 mumol/l (therapeutic range) was less than 10%. The correlation between extractions from venous whole blood and capillary blood applied to chromatographic paper was more than 0.94. The analytes were stable in dried blood spots for at least fifty days at -20 degrees C. The decrease of concentration was less than 10%, when the paper was stored at 37 degrees C for fifty days. The assay is reliable and easy to use for therapeutic monitoring of mefloquine with a lower limit of determination of 0.3-0.5 mumol/l.

Chromatography, High Pressure Liquid↗
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↗
PubMed1992

Effect of different fractions of heparin on Plasmodium falciparum merozoite invasion of red blood cells in vitro.

Heparin and various heparin fractions were separated according to differences in molecular weight or affinity for antithrombin III and used for the inhibition of Plasmodium falciparum merozoite invasion of red blood cells in vitro. No variation in sensitivity to heparin was found among the four strains of P. falciparum tested; all required approximately 5 micrograms/ml (0.5 U/ml) of heparin for 50% inhibition of invasion. The most efficient fraction of heparin was the one with low affinity for antithrombin III. Its 50% inhibition concentration was 1 microgram/ml, indicating that it was more efficient than unfractionated heparin and other heparin fractions. The effect of heparin was reversible, since washing of heparin-treated cultures containing mainly schizonts showed no inhibition of merozoite invasion. The results suggest that a heparin fraction with no anticoagulant effect might be useful in the treatment of patients with falciparum malaria.

Animals↗
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↗