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Biomedical subjects

L Rombo

Publications and source records attributed to L Rombo.

98 records · Page 6Linked to original sources
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Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid during treatment of Trypanosoma gambiense infection in Côte d'Ivoire.

Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid (CSF) were determined in 11 patients with Trypanosoma gambiense infection without involvement of the central nervous system in Côte d'Ivoire. Blood samples were drawn during a 48 h period after the first and last dose of pentamidine dimesylate given as 10 intramuscular injections on alternate days. Maximum plasma concentrations were generally attained within one hour after injection but varied extensively (420-13420 nmol/litre). The median plasma concentration 48 h after the last dose was approximately 5 times higher than that after the first dose. The ratio between whole blood and plasma concentration was approximately 2. Small amounts of the drug were found in the CSF after the last dose. The findings showed inter-individual differences in the pharmacokinetics of pentamidine. The currently recommended daily dose regimen could be questioned, as drug accumulation was pronounced. All patients were cured and the concentrations attained should be considered as parasiticidal. Further studies on the kinetics and distribution after single and multiple doses of pentamidine as well as studies on the possible relationship between adverse effects and plasma concentrations are, however, needed.

Adolescent↗
PubMedDate not supplied

Long-term exposure of Trypanosoma brucei gambiense to pentamidine in vitro.

In order to study the sensitivity in vitro of Trypanosoma brucei gambiense to pentamidine, 5 x 10(4) parasites were exposed to 0, 0.1, 1.0, 2.0, 10, 100, 1000 and 10,000 micrograms/L of pentamidine isethionate for up to 10 d. The viability of parasites was determined each day by microscopy. Multiplication was retarded during continuous exposure to 2 micrograms/L. After 4 d no further multiplication took place, although the trypanosomes remained alive for another 3 d. The parasiticidal effect was more pronounced when higher concentrations were used; when exposed to 10 and 100 micrograms/L, all parasites were dead after 4 and 3 d, respectively. Despite exposure to 1000 micrograms/L, 74% of the parasites were still alive the next day. 10,000 micrograms/L killed all parasites within 24 h of exposure. Our results show that the time period of exposure to pentamidine plays a major role in determining the sensitivity in vitro of T. b. gambiense, and we suggest that prolonged exposure in vivo may be more important than attaining high but brief peak concentrations.

Animals↗
PubMedDate not supplied

Susceptibility of Plasmodium falciparum to quinine in vitro: effects of drug concentrations and time of exposure.

We have studied the relationship between quinine concentrations ranging from 0.16 to 332 mumol/L in a blood-medium mixture and the time of exposure (12-168 h) needed for inhibition of Plasmodium falciparum (F32 strain) in continuous culture. When we exposed the parasites for 12 h, only brief inhibition was observed. After 24 h of exposure, parasites were inhibited for 2-3 d at quinine concentrations > or = 10.4 mumol/L. With 48 and 72 h of exposure, the inhibition lasted for 6-8 d at concentrations > or = 1.3 mumol/L and for 8-11 d at concentrations between 2.6 and 166 mumol/L. After 96 h of exposure, parasites were inhibited for 11-17 d at concentrations > or = 0.65 mumol/L. With 168 h of exposure, parasites were inhibited at all quinine concentrations > or = 0.65 mumol/L during 28 d of post-exposure cultivation. After reappearance, parasites multiplied on average 7.6 fold during each parasite schizogony cycle. The calculated parasite elimination rate in the presence of effective concentrations of quinine was 99.7-99.9% per cycle. We conclude that the elimination rate of the parasites is concentration-dependent at low concentrations of quinine in vitro. As soon as a threshold concentration of 0.65-2.6 mumol/L is attained, only the exposure time determines parasite elimination. These experiments suggest that it might be preferable to reduce each dose rather than the duration of treatment in areas where P. falciparum is susceptible to quinine.

Animals↗
PubMedDate not supplied

Comparison of 3, 5 and 7 days' treatment with Quinimax for falciparum malaria in Guinea-Bissau.

For treatment of malaria, the World Health Organization recommends 10 mg of quinine per kg body-weight 3 times a day for at least 7 d. In Guinea-Bissau, as in several other African countries, a 3 d treatment regimen (10 mg/kg twice daily) is currently used. We therefore compared the 3 d treatment period with periods of 5 and 7 d. A total of 145 children with clinical malaria due to monoinfection with Plasmodium falciparum, with > or = 20 parasites per 200 leucocytes, were treated with intramuscular Quinimax 10 mg per kg body-weight twice daily for 3, 5 or 7 d. The children were then examined once weekly for 4 weeks. Following the 3 d treatment regimen, 34 of 43 children (79%) had parasitaemia on day 28 or before; following the 5 d treatment regimen, 36 of 40 children (90%) did so; and following the 7 d treatment regimen, 7 of 62 children (11%) were parasitaemic at that time. This study thus suggests that the currently recommended 3 d Quinimax treatment regimen in Guinea-Bissau for moderate and severe malaria is not effective.

Adolescent↗
PubMedDate not supplied

Low-dose quinine for treatment of Plasmodium falciparum malaria in Guinea-Bissau.

The recommended dose of 10 mg quinine/kg bodyweight 3 times a day for 7 days for treatment of malaria is so high that many patients experience cinchonism. We have earlier obtained good results with 7 days' treatment with 20 mg Quinimax/kg bodyweight divided into 2 daily doses. In order to identify the lowest effective dose, children with symptomatic malaria were treated with quinine twice a day for 7 days. They were assigned to 1 of 3 groups treated daily with 10 mg/kg, 15 mg/kg, or 20 mg/kg bodyweight, respectively; 42, 46, and 34 children, respectively, received treatment and completed 5 weeks of follow-up. The cumulative percentages of all children with parasitaemia during follow-up on day 28 or before were 33%, 13% and 12%, respectively. Treatment with 10 mg quinine salt/kg daily for 7 days gave a significantly higher rate of recrudescence than did treatment with 15 or 20 mg/kg daily. Thus at least 15 mg of quinine salt/kg bodyweight daily should be recommended for treatment of symptomatic Plasmodium falciparum malaria in Guinea-Bissau.

Adolescent↗