Efficacy of a 14-day primaquine regimen in preventing relapses in patients with Plasmodium vivax malaria in Mumbai, India

Rajgor, Dimple; Nj, Gogtay; Kadam, Vaijayanti; Kamtekar, K.D.; Dalvi, S. S.; Chogle, Arun R; Aigal, U; Bichile, Lata; Kain, Kevin C.; Na, Kshirsagar

doi:10.1016/s0035-9203(03)90082-4

Cited by 29 publications

(28 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To better understand PQ metabolism, PQ degradation by microbial enzymes was studied and two new dimeric metabolites of PQ (20,21) were identified [156,157]. These dimers of N-acetylprimaquine were inactive in vitro as anti-malarials, thus reinforcing the idea that the free primary amino group on the aliphatic chain of PQ is essential for anti-malarial activity [156,157].…”

Section: Dimeric Compoundsmentioning

confidence: 96%

“…Similarly, the paediatric doses can be increased from 0.25 to 0.5 mg/kg/d, according to the parasite strain that prevails at the site of exposure. The beginning of terminal prophylaxis with PQ should coincide with the last 2 weeks of prophylactic administration of schizontoxides doxycycline, mefloquine or chloroquine or with the final week of prophylaxis with atovaquone-proguanil [14,19,20].…”

Section: Terminal Prophylaxis or Partmentioning

confidence: 99%

“…Some have argued that this phenomenon may arise from an association of physical, chemical or biological properties of the drug, together with its low half-life or ability to sterilise the parasite's gametocytes [9]. Since 1961, PQ is known to elicit some resistance from asexual blood stages of P. vivax, but such is of no clinical consequence [20]. Some clinical evidences of PQ resistance are occasionally reported, but their detection is rare.…”

Section: Parasitic Resistancementioning

confidence: 99%

See 2 more Smart Citations

Primaquine revisited six decades after its discovery

Vale¹,

Moreira²,

Gomes³

2009

European Journal of Medicinal Chemistry

321

308

View full text Add to dashboard Cite

Section: Dimeric Compoundsmentioning

confidence: 96%

Section: Terminal Prophylaxis or Partmentioning

confidence: 99%

Section: Parasitic Resistancementioning

confidence: 99%

See 1 more Smart Citation

Primaquine revisited six decades after its discovery

Vale¹,

Moreira²,

Gomes³

2009

European Journal of Medicinal Chemistry

321

308

View full text Add to dashboard Cite

“…PQ synthetic methods yield a racemic mixture of these two enantiomers; when PQ was developed, enantiomeric separation of racemates was not available, and single enantiomers of racemic drugs were not the norm in drug development. Later, when the next generation of 8-AQs, namely, bulaquine (Rajgor et al, 2003;Krudsood et al, 2006) and tafenoquine (TQ) (Crockett and Kain, 2007;Llanos-Cuentas et al, 2014), were developed, the same side chain was retained. Thus, PQ is still available as the racemate, and TQ is also being developed as a racemate (LlanosCuentas et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Pharmacokinetics of Primaquine in Healthy Human Volunteers

et al. 2015

View full text Add to dashboard Cite

Primaquine (PQ), a racemic drug, is the only treatment available for radical cure of relapsing Plasmodium vivax malaria and blocking transmission of P. falciparum malaria. Recent studies have shown differential pharmacologic and toxicologic profiles of individual PQ enantiomers in rodent, dog, and primate animal models. This study was conducted in six healthy adult human volunteers to determine the plasma pharmacokinetic profile of enantiomers of PQ and carboxyprimaquine (cPQ), the major plasma metabolite. The individuals were orally administered PQ diphosphate, equivalent to 45-mg base, 30 minutes after a normal breakfast. Blood samples were collected at different time intervals, and plasma samples were analyzed for enantiomers of PQ and cPQ. Plasma PQ concentrations were low and variable for both parent enantiomers and peaked around 2-4 hours. Peak (2)-(R)-PQ concentrations ranged from 121 ng/ml to 221 ng/ml, and peak (+)-(S)-PQ concentrations ranged from 168 ng/ml to 299 ng/ml. The cPQ concentrations were much higher and were surprisingly consistent from subject to subject. Essentially all the cPQ detected in plasma was (2)-cPQ. The peak concentrations of (2)-cPQ were observed at 8 hours (range: 1104-1756 ng/ml); however, very high concentrations were sustained through 24 hours. (+)-cPQ was two orders of magnitude lower than (2)-cPQ, and in a few subjects it was detected but only under the limit of quantification. In vitro studies with primary human hepatocytes also suggested more rapid metabolism of (2)-PQ compared with (+)-PQ. The results suggest more rapid metabolism of (2)-PQ to (2) cPQ compared with (+)-PQ. Alternatively, (+)-PQ or (+)-cPQ could be rapidly converted to another metabolite(s) or distributed to tissues. This is the first clinical report on enantioselective pharmacokinetic profiles of PQ and cPQ and supports further clinical evaluation of individual PQ enantiomers.

show abstract

“…[20][21][22][23][24] In this study, late primary attacks occurred in individuals who had received primaquine prophyt t laxis regularly, and it is thus possible that factors such as inadequate primaquine dosage and absorption are associated with P. vivax malaria. However, only 0.4% of those receiving the standard prophylactic dose of primaquine were rettreated for relapse, suggesting that primaquine effectively reduces the incit t dence of late primary attacks.…”

Section: Discussionmentioning

confidence: 75%

Chemoprophylaxis and the epidemiological characteristics of re-emergent P. vivax malaria in the Republic of Korea

Kim

Shin

Yong

et al. 2006

Bull World Health Organ

View full text Add to dashboard Cite

Objective In the Republic of Korea (ROK), soldiers stationed where there is a risk of contracting malaria have received antimalarial chemoprophylaxis since 1997. However, chemoprophylaxis may facilitate the development of drug resistance, and late primary attacks in individuals who have received chemoprophylaxis are becoming more frequent. We investigated the association between chemoprophylaxis and the epidemiological characteristics and effectiveness of treatment for re-emergent Plasmodium vivax malaria, using a nationwide malaria database. Methods Among soldiers at risk of malaria between 1999 and 2001, we reviewed all P. vivax malaria cases (1158) that occurred before 31 December 2003. Early and late primary attacks were defined as cases occurring < 2 or > 2 months after the last day of exposure to risk of malaria, respectively. Findings Of these cases, 634 (72.0%) had received chemoprophylaxis, and 324 (28.0%) had not. Cases occurred mostly in summer, with a peak in July-August. Stratification by chemoprophylaxis history revealed different times to onset. Early primary attacks were more prevalent in the group not receiving chemoprophylaxis, while in the group receiving chemoprophylaxis most cases were late primary attacks. Of the latter, 312 out of 461 (67.7%) did not take primaquine regularly. After treatment of the first attack, 14 (1.2%) of 1158 were re-treated; all re-treated cases were cured using the same doses and regimen used for the first treatment. Conclusion In ROK, the increase in late primary episodes of re-emergent P. vivax malaria is associated with the use of antimalarial chemoprophylaxis.Bulletin of the World Health Organization 2006;84:827-834.Voir page 833 le résumé en français. En la página 833 figura un resumen en español. IntroductionPlasmodium vivax, the causative agent of vivax malaria, has been endemic in the Republic of Korea (ROK) for cent t turies. The number of cases of endemic malaria began to decline in the 1960s, partly due to increased socioeconomic development, increased use of agricult t tural pesticides, and the efforts of the National Malaria Eradication Service. These factors contributed to the eradicat t tion of malaria in the ROK, resulting in the declaration by WHO in 1979 that the country was malariatfree. 1 In 1993, one case of malaria attributed to autot chthonous transmission was detected near the demilitarized zone (DMZ) that separates ROK (south) from the Democratic People's Republic of Korea (north).2 Since 1993, the number of malaria cases has increased exponentially, particularly among soldiers based near the DMZ. [1][2][3][4][5] Chemoprophylaxis and the epidemiological characteristics of re-emergent P. vivax malaria in the Republic of Korea In ROK, healthy males aged over 18 years serve 26 months of mandat t tory military duty; most are stationed throughout their service near the DMZ, where the risk of malaria is highest. After finishing their military duty, the soldiers return from these risk areas to areas with little or no malaria. To reduce the occurren...

show abstract

Efficacy of a 14-day primaquine regimen in preventing relapses in patients with Plasmodium vivax malaria in Mumbai, India

Cited by 29 publications

References 10 publications

Primaquine revisited six decades after its discovery

Primaquine revisited six decades after its discovery

Enantioselective Pharmacokinetics of Primaquine in Healthy Human Volunteers

Chemoprophylaxis and the epidemiological characteristics of re-emergent P. vivax malaria in the Republic of Korea

Contact Info

Product

Resources

About