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Studies on the chemotherapy of malaria. V. The suppression of malaria by amodiaquin (camoquin)

EDESON JF, TURNER LH, LAING AB

Med J Malaya, 1955 Jun;9(4):260-4.

PMID: 13253125

Matched MeSH terms: Amodiaquine*

Studies on the chemotherapy of malaria. IV. The treatment of acute malaria with amodiaquin (camoquin)

EDESON JF, WILSON T, TURNER LH, LAING AB

Med J Malaya, 1955 Jun;9(4):252-9.

PMID: 13253124

Matched MeSH terms: Amodiaquine*

Validation of high performance liquid chromatography-electrochemical detection methods with simultaneous extraction procedure for the determination of artesunate, dihydroartemisinin, amodiaquine and desethylamodiaquine in human plasma for application in clinical pharmacological studies of artesunate-amodiaquine drug combination

Lai CS, Nair NK, Muniandy A, Mansor SM, Olliaro PL, Navaratnam V

J Chromatogr B Analyt Technol Biomed Life Sci, 2009 Feb 15;877(5-6):558-62.

PMID: 19147417 DOI: 10.1016/j.jchromb.2008.12.037

With the expanded use of the combination of artesunate (AS) and amodiaquine (AQ) for the treatment of falciparum malaria and the abundance of products on the market, comes the need for rapid and reliable bioanalytical methods for the determination of the parent compounds and their metabolites. While the existing methods were developed for the determination of either AS or AQ in biological fluids, the current validated method allows simultaneous extraction and determination of AS and AQ in human plasma. Extraction is carried out on Supelclean LC-18 extraction cartridges where AS, its metabolite dihydroartemisinin (DHA) and the internal standard artemisinin (QHS) are separated from AQ, its metabolite desethylamodiaquine (DeAQ) and the internal standard, an isobutyl analogue of desethylamodiaquine (IB-DeAQ). AS, DHA and QHS are then analysed using Hypersil C4 column with acetonitrile-acetic acid (0.05M adjusted to pH 5.2 with 1.00M NaOH) (42:58, v/v) as mobile phase at flow rate 1.50ml/min. The analytes are detected with an electrochemical detector operating in the reductive mode. Chromatography of AQ, DeAQ and IB-DeAQ is carried out on an Inertsil C4 column with acetonitrile-KH(2)PO(4) (pH 4.0, 0.05M) (11:89, v/v) as mobile phase at flow rate 1.00ml/min. The analytes are detected by an electrochemical detector operating in the oxidative mode. The recoveries of AS, DHA, AQ and DeAQ vary between 79.1% and 104.0% over the concentration range of 50-1400ng/ml plasma. The accuracies of the determination of all the analytes are 96.8-103.9%, while the variation for within-day and day-to-day analysis are <15%. The lower limit of quantification for all the analytes is 20ng/ml and limit of detection is 8ng/ml. The method is sensitive, selective, accurate, reproducible and suited particularly for pharmacokinetic study of AS-AQ drug combination and can also be used to compare the bioavailability of different formulations, including a fixed-dose AS-AQ co-formulation.

Matched MeSH terms: Amodiaquine/administration & dosage; Amodiaquine/analogs & derivatives*; Amodiaquine/blood; Amodiaquine/pharmacokinetics; Amodiaquine/pharmacology

In-vitro inhibitory effect of Tualang honey on cytochrome P450 2C8 activity

Muthiah YD, Ong CE, Sulaiman SA, Tan SC, Ismail R

J Pharm Pharmacol, 2012 Dec;64(12):1761-9.

PMID: 23146039 DOI: 10.1111/j.2042-7158.2012.01551.x

To investigate the effect of Tualang honey on cytochrome P450 2C8 (CYP2C8) activity in vitro using an amodiaquine N-desethylase assay.

Matched MeSH terms: Amodiaquine/analogs & derivatives; Amodiaquine/metabolism*

Fulltext Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis

Naing C, Whittaker MA, Htet NH, Aye SN, Mak JW

PLoS One, 2019;14(12):e0225882.

PMID: 31856172 DOI: 10.1371/journal.pone.0225882

BACKGROUND: The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that assessed comparisons of ACTs for treating uncomplicated falciparum malaria reported conflicting results in treatment efficacy. A network meta-analysis is an extension of pairwise meta-analysis that can synthesize evidence simultaneously from both direct and indirect treatment comparisons. The objective was to synthesize evidence on the comparative efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region.

METHODS: Relevant randomized trials that assessed efficacy of antimalarial drugs for patients having uncomplicated falciparum malaria in Asian region were searched in health-related databases. We evaluated the methodological quality of the included studies with the Cochrane risk of bias tool. Main outcome was treatment success at day 28 as determined by the absence of parasiteamia. We performed network meta-analysis of the interventions in the trials, and assessed the overall quality of evidence using the GRADE approach.

RESULTS: Seventeen randomized trials (n = 5043) were included in this network meta-analysis study. A network geometry was formed with 14 antimalarial treatment options such as artemether-lumefantrine (AL), artemisinin-piperaquine, artesunate-amodiaquine, artesunate-mefloquine (ASMQ), artesunate-chloroquine, artesunate-mefloquine home treatment, artesunate-mefloquine 2-day course, artesunate plus sulfadoxine-pyrimethamine, chloroquine, dihydroartemisinin-piperaquine (DHP), dihydroartemisinin-piperaquine home treatment, dihydroartemisinin-piperaquine 4-day course, dihydroartemisinin-piperaquine and added artesunate, sulfadoxine-pyrimethamine. A maximum number of trials included was DHP compared to ASMQ (n = 5). In general, DHP had better efficacy than AL at day 28 (DHP vs AL: OR 2.5, 95%CI:1.08-5.8). There is low certainty evidence due to limited number of studies and small trials.

DISCUSSION/ CONCLUSIONS: The findings suggest the superiority of DHP (3-day course) to AL and other comparator ACTs are with the overall low/very low quality of evidence judgements. Moreover, one drug regimen is better than another is only if current drug-resistance patterns are at play. For example, the AL might be better than DHP in areas where both artemisinin and piperaquine resistance patterns are prevalent. For substantiation, well-designed larger trials from endemic countries are needed. In the light of benefit versus harm concept, future analysis with safety information is recommended.

Matched MeSH terms: Amodiaquine

Fulltext Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine in Malaysian healthy normal volunteers

Navaratnam V, Ramanathan S, Wahab MS, Siew Hua G, Mansor SM, Kiechel JR, et al.

Eur J Clin Pharmacol, 2009 Aug;65(8):809-21.

PMID: 19404632 DOI: 10.1007/s00228-009-0656-1

There is limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria. This study examines the bioavailability and tolerability of a fixed (200 mg artesunate + 540 mg amodiaquine) and loose (200 mg + 612 mg) combination with a 2x2 cross-over design in 24 healthy volunteers.

Matched MeSH terms: Amodiaquine/adverse effects*; Amodiaquine/blood; Amodiaquine/pharmacokinetics*

Gene, ethnic and gender influences predisposition of adverse drug reactions to artesunate among Malaysians

Yusof W, Hua GS

Toxicol. Mech. Methods, 2012 Apr;22(3):184-92.

PMID: 22003869 DOI: 10.3109/15376516.2011.623331

Artesunate (AS) and amodiaquine (AQ) are two prodrugs widely used as antimalarial agents and are metabolized by the CYP P450 2A6 (CYP 2A6) and CYP P450 2C8 (CYP 2C8) enzymes, respectively.

Matched MeSH terms: Amodiaquine/adverse effects*; Amodiaquine/metabolism

High prevalence of CYP2A6*4 and CYP2A6*9 alleles detected among a Malaysian population

Yusof W, Gan SH

Clin Chim Acta, 2009 May;403(1-2):105-9.

PMID: 19361454 DOI: 10.1016/j.cca.2009.01.032

CYP2A6 gene encodes the principal enzyme involved in the metabolism of many drugs including artesunate. We developed a simplified duplex nested PCR method for the detection of the CYP2A61B, CYP2A62, CYP2A64, CYP2A67, CYP2A68 and CYP2A69 variant alleles highly prevalent among Malaysian population.

Matched MeSH terms: Amodiaquine/administration & dosage; Amodiaquine/therapeutic use

Prophylactic and sporontocidal treatment of chloroquine resistant Plasmodium falciparum from Malaya

Clyde DF, DuPont HL, Miller RM, McCarthy VC

Trans R Soc Trop Med Hyg, 1970;64(6):834-8.

PMID: 4924648

Matched MeSH terms: Amodiaquine/therapeutic use

Characterisation of a drug resistant strain of Plasmodium falciparum from Sabah

Clyde DF, McCarthy VC, Gilman RH, Miller RM

J Trop Med Hyg, 1973 Sep;76(9):226-30.

PMID: 4582746

Matched MeSH terms: Amodiaquine/therapeutic use

Fulltext Heterologous Expression of a Novel Drug Transporter from the Malaria Parasite Alters Resistance to Quinoline Antimalarials

Tindall SM, Vallières C, Lakhani DH, Islahudin F, Ting KN, Avery SV

Sci Rep, 2018 02 06;8(1):2464.

PMID: 29410428 DOI: 10.1038/s41598-018-20816-0

Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.

Matched MeSH terms: Amodiaquine/pharmacology

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