Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Pharmacology

Pharmacokinetics and Bioequivalence Evaluation of Two Fixed-Dose Tablet Formulations of Dihydroartemisinin and Piperaquine in Vietnamese Subjects

Nguyen Trong Chinh, Nguyen Ngoc Quang, Nguyen Xuan Thanh, Bui Dai, Jason P. Geue, Russell S. Addison, Thomas Travers, Michael D. Edstein
Nguyen Trong Chinh
1Department of Infectious Diseases, Military Hospital 108, Hanoi, Vietnam
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nguyen Ngoc Quang
1Department of Infectious Diseases, Military Hospital 108, Hanoi, Vietnam
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nguyen Xuan Thanh
2Department of Malaria, Military Institute of Hygiene and Epidemiology, Hanoi, Vietnam
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bui Dai
2Department of Malaria, Military Institute of Hygiene and Epidemiology, Hanoi, Vietnam
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason P. Geue
3TetraQ, Royal Brisbane and Women's Hospital, Brisbane, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Russell S. Addison
3TetraQ, Royal Brisbane and Women's Hospital, Brisbane, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Travers
4Australian Army Malaria Institute, Brisbane, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael D. Edstein
4Australian Army Malaria Institute, Brisbane, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: mike.edstein@defence.gov.au
DOI: 10.1128/AAC.00927-08
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

The two fixed-dose combinations of dihydroartemisinin and piperaquine (Artekin and Arterakine) were found to be bioinequivalent in healthy Vietnamese subjects. However, because the peak plasma concentrations and areas under the concentration-time curves of dihydroartemisinin and piperaquine were only marginally different between the two formulations, similar therapeutic efficacies are expected in the treatment of malaria infections.

Artemisinin-based combination treatments (ACTs) are now considered the best therapy for the treatment of Plasmodium falciparum malaria (13, 19). One of the most promising ACTs is the fixed-dosed dihydroartemisinin-piperaquine combination marketed as Artekin (Holleykin Pharmaceuticals Co. Ltd., China), which is well tolerated and highly effective in the treatment of P. falciparum malaria (2, 3, 8, 14). The cure rate for Artekin is typically greater than 95% following a 3-day course, with a 42-day follow-up period. Despite the availability of clinical data on the efficacy of Artekin, no pharmacokinetic data are available on dihydroartemisinin given as an oral coformulation with piperaquine and few data are available on the disposition of piperaquine following Artekin administration.

Recently, the Vietnamese Ministry of Health licensed Central Pharmaceutical Company No. 1 to produce a fixed-dose combination of dihydroartemisinin-piperaquine, marketed as Arterakine, for use in Vietnam. In the present study, we compared the pharmacokinetics of the components of Artekin and Arterakine and assessed the bioequivalence of Arterakine to the reference formulation, Artekin.

A randomized, open-label, single-dose, two-period crossover study was carried out with 24 healthy male Vietnamese subjects with a mean (± standard deviation) age of 21.0 (2.7) years and a mean weight of 59.7 (3.3) kg. Each subject received three tablets of the reference drug, Artekin (batch no. 20040201; each tablet contains 40 mg dihydroartemisinin and 320 mg piperaquine phosphate; Holleykin Pharmaceutical Co. Ltd., Guangdong, China), and three tablets of the test drug, Arterakine (batch no. 010606; each tablet contains 40 mg dihydroartemisinin and 320 mg piperaquine phosphate; Central Pharmaceutical Factory No. 1, Hanoi, Vietnam). The study was carried out within the 3-year expiration period of the medication, and the washout period between the two treatment phases was 10 weeks. The study was approved by the Review and Scientific Board of Central Military Hospital 108 and the Australian Defense Human Research Ethics Committee (ADHREC 437/06).

Each subject received the medication after an overnight fast (no food for 8 h), and the tablets were taken with 200 ml of water. Food was withheld for 4 h after drug administration. Beverages containing caffeine, alcohol, or grapefruit juice and smoking were not allowed 2 days before and after drug administration. Venous blood samples (7 ml) were collected with an indwelling cannula within 0.5 h (baseline) prior to dosing and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 h after drug administration. Subsequent blood samples were collected by venipuncture at days 1, 3, 7, 14, 21, and 28 after dosing. Blood samples were centrifuged, and the separated plasma samples (3 ml) were stored at −80°C until analyzed, which was within 12 months of collection.

Plasma concentrations of dihydroartemisinin were measured by liquid chromatography-tandem mass spectrometry. Briefly, to a glass tube fitted with a Teflon-lined cap were added plasma (200 μl) and alprazolam (internal standard, 50 μl of a 150-ng/ml concentration) and the contents were mixed prior to the addition of butyl chloride-ethyl acetate (9:1, vol/vol; 3 ml). The tubes were rotated for 5 min and then centrifuged (3,000 × g for 5 min). The organic layer was transferred to a clean glass tube and evaporated to dryness under a stream of air at 37°C. Chromatographic analysis was conducted with a Prominence liquid chromatography system (Shimadzu, Japan) and an HTC PAL autosampler (CTC Analytics, Switzerland) linked to an API3200 mass spectrometer (Applied Biosystems) fitted with an electrospray interface operated in the positive-ion mode. The reconstituted sample was separated on a Luna C18 high-performance liquid chromatography column (50 by 2.0 mm [inside diameter], 3-μm particle size; Phenomenex) preceded by a Luna C18 guard cartridge with an acetonitrile-ammonium acetate gradient at a flow rate of 0.4 ml/min. The peak area ratios of the NH+ adduct of dihydroartemisinin (product at m/z 267.2 from the parent ion at m/z 302.2) to the internal standard (product at m/z 281.2 from the parent ion at m/z 309.2) were calculated for each sample from the measured peak areas obtained by selected reaction monitoring. The retention times of the internal standard and dihydroartemisinin were 2.0 and 2.2 min, respectively. Quadratic regression of the concentration data (range, 1 to 1,000 ng/ml) with 1/concentration2 (χ2) weighting yielded a correlation coefficient of >0.994 for dihydroartemisinin. The lower limit of quantification was 1 ng/ml with 0.2 ml of plasma. The overall precision of analysis for dihydroartemisinin, as defined by the percent coefficient of variation of spiked samples was 6.3% at 1 ng/ml, 5.7% at 20 ng/ml, 4.6% at 200 ng/ml, and 6.6% at 750 ng/ml. The corresponding inaccuracy values were −1.3%, −1.5%, −0.7%, and 3.2%. Plasma concentrations of piperaquine were measured by a validated high-performance liquid chromatography method (10). The precision of the assay was 10.3% at 10 ng/ml, 6.8% at 100 ng/ml, and 6.7% at 500 ng/ml. The corresponding inaccuracy values were 11%, 3%, and 1%. The lower limit of quantification of piperaquine was 5 ng/ml with 0.5 ml of plasma.

Pharmacokinetic parameters (peak concentration [Cmax], time to reach maximum concentration [Tmax], area under the concentration-time curve from 0 h to the last data point [AUC0→last] and from the last data point to infinity [AUClast→∞], terminal half-life [t1/2], apparent oral clearance [CL/F], and apparent volume of distribution [V/F]) were determined from the plasma concentration-time data by noncompartmental methods (5). The pharmacokinetic parameters of dihydroartemisinin and piperaquine were calculated from the nominal potency of the tablets and tested parametrically with the paired t test for statistically significant differences between the two formulations. Schuirmann's two one-sided t test procedure was used to calculate the 90% confidence interval (CI) from the log-transformed pharmacokinetic data (15). Treatments were considered bioequivalent if the 90% CI for mean point estimators (ratio of test/reference) for the Cmax and AUC of dihydroartemisinin and piperaquine fell within the acceptance range of 80 to 125% for log-transformed values (4). The effects of formulation, period, and sequence effects were studied by analyses of variance (ANOVA) of the log-transformed data.

The mean plasma concentration-time profiles of dihydroartemisinin after a single oral dose of Arterakine and Artekin are shown in Fig. 1, and the pharmacokinetics of dihydroartemisinin are summarized in Table 1.The geometric mean Cmax of dihydroartemisinin was higher and was achieved marginally faster after Arterakine (Cmax, 198 ng/ml; mean Tmax, 1.0 h) than after Artekin (Cmax, 159 ng/ml; Tmax, 1.5 h) administration. The AUC0→last of dihydroartemisinin was higher after Arterakine than after Artekin administration, with geometric mean values of 442 and 366 ng·h/ml, respectively, but the difference was not significant (P > 0.05). Dihydroartemisinin was rapidly eliminated, with a t1/2 of about 1 h for the two formulations. There was a significant difference in the CL/F (4.95 versus 5.87 liters/h/kg; 95% CI, −1.72, −0.12; P = 0.03) and V/F of dihydroartemisinin (7.00 versus 8.02 liters/kg; 95% CI, −3.10, −0.13; P = 0.03) following the administration of the two formulations. Overall, the pharmacokinetics of dihydroartemisinin after Arterakine or Artekin administration were comparable to values obtained in healthy Vietnamese and Thai subjects given dihydroartemisinin alone (9, 11). Thus, piperaquine does not appear to alter the pharmacokinetics of dihydroartemisinin when given as a coformulation.

The mean plasma concentration-time profiles and pharmacokinetics of piperaquine are presented in Fig. 2 and Table 1, respectively. The geometric mean Cmax (232 versus 204 ng/ml) and AUC0→last (13,431 versus 11,988 ng · h/ml) of piperaquine were higher after Arterakine than after Artekin administration, but the difference was not significant. After adjusting for dose and weight differences, the Cmax of piperaquine was markedly higher in the healthy Vietnamese subjects after the administration of both ACTs than in healthy Caucasians administered piperaquine alone (1, 16). Ethnic differences and differences in tablet excipients and dissolution behavior may account for the variations in piperaquine concentrations achieved after the administration of piperaquine alone and the two coformulations used in the present study. The elimination of piperaquine (based on measurements from day 7 forward) was lengthy, with an estimated mean t1/2 of about 645 h (26.8 days) in the healthy subjects, which is in good agreement with values obtained in healthy Vietnamese (6, 12) and Caucasian subjects (16, 18) and in malaria patients (7, 17). The mean CL/Fs of piperaquine after Arterakine and Artekin administration of 0.42 and 0.50 liter/h/kg, respectively, were lower than previously reported in healthy Vietnamese (0.74 liter/h/kg [12]) and Caucasian subjects (1.14 liters/h/kg [16]) given piperaquine alone. A large V/F of piperaquine was estimated after Arterakine (377 ± 125 liter/kg) and Artekin (428 ± 170 liter/kg) administration, which is consistent with the high values reported in healthy subjects (6, 12, 16) and malaria patients (7, 17).

Statistical evaluation of the pharmacokinetic data for dihydroartemisinin and piperaquine showed bioinequivalence of Arterakine and Artekin for the Cmax, AUC0→last, and AUC0→∞ of dihydroartemisinin and the Cmax and AUC0→∞ of piperaquine within the predetermined acceptance range of 80 to 125% at the 90% CI (Table 2). The results of the ANOVA found that formulation, period, and sequence had no statistically significant effects on the Cmax of dihydroartemisinin and piperaquine. However, there was a significant effect of formulation on the AUC0→last of dihydroartemisinin (P = 0.01) and piperaquine (P = 0.04). Similarly, there was a significant effect of period on the AUC0→last of dihydroartemisinin (P = 0.02) and piperaquine (P = 0.03), which may be a random occurrence but is unlikely to be of importance given the balanced study design. The sequence had no significant effect on the AUC0→last of either drug.

The mean drug contents based on five tablets of Arterakine were 103.3% ± 4.4% for dihydroartemisinin and 100.6% ± 1.2% for piperaquine. The corresponding contents in the Artekin tablets were 95.3% ± 8.3% and 98.8% ± 2.9%. Although the lower contents of dihydroartemisinin (8%) and piperaquine (1.8%) in the Artekin than in the Arterakine tablets would have contributed to the bioinequivalence of the two formulations, after adjustment for drug content, the Cmax and AUC0→∞ of both drugs were still outside the acceptance range of 80 to 125% (data not shown).

In conclusion, the pharmacokinetic parameters of dihydroartemisinin and piperaquine and the values obtained were consistent with previous studies in which the drugs were given alone. Because the bioavailability of dihydroartemisinin and piperaquine was only marginally higher after Arterakine than after Artekin administration, the two formulations are expected to result in similar therapeutic efficacies in the treatment of malaria infections.

FIG. 1.
  • Open in new tab
  • Download powerpoint
FIG. 1.

Mean (standard error of the mean) plasma dihydroartemisinin concentration-time profiles following the administration of a single oral dose of three Arterakine (•) or Artekin (○) tablets to 24 healthy Vietnamese subjects.

FIG. 2.
  • Open in new tab
  • Download powerpoint
FIG. 2.

Mean (standard error of the mean) plasma piperaquine concentration-time profiles following the administration of a single oral dose of three Arterakine (•) or Artekin (○) tablets to 24 healthy Vietnamese subjects.

View this table:
  • View inline
  • View popup
TABLE 1.

Pharmacokinetic parameters of dihydroartemisinin and piperaquine in 24 healthy Vietnamese subjects following the administration of a single oral dose of 120 mg dihydroartemisinin and 960 mg piperaquine in the form of three Arterakine or three Artekin tablets (reference formulation)a

View this table:
  • View inline
  • View popup
TABLE 2.

Parametric 90% CIs for the mean pharmacokinetic properties of dihydroartemisinin and piperaquine after the administration of a single oral dose of Arterakine and Artekin (reference formulation)

ACKNOWLEDGMENTS

This study was carried out under the auspices of the Vietnam Australia Defense Malaria Project, a defense cooperation between the Vietnam People's Army and the Australian Defense Force. We thank the Vietnam People's Army Department of Military Medicine for supporting this study and the financial sponsor, the Australian Defense Force International Policy Division.

We thank Ric Price for providing the Artekin tablets, Le Ngoc Anh for administrative-logistic support, and Chu Xuan Anh for coordinating staff in the collection and processing of blood samples. We are most grateful to Steve Wallis for performing the ANOVA and to G. Dennis Shanks and Bob Cooper for comments on the manuscript.

The opinions expressed in this report are ours and do not necessarily reflect those of the Defense Health Service or any extant Australian Defense Force policy.

FOOTNOTES

    • Received 11 July 2008.
    • Returned for modification 3 November 2008.
    • Accepted 22 November 2008.
  • Copyright © 2009 American Society for Microbiology

REFERENCES

  1. 1.↵
    Ahmed, T., P. Sharma, A. Gautam, B. Varshney, M. Kothari, S. Ganguly, J. J. Moehrle, J. Paliwal, N. Saha, and V. Batra. 2008. Safety, tolerability, and single- and multiple-dose pharmacokinetics of piperaquine phosphate in healthy subjects. J. Clin. Pharmacol.48:166-175.
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    Ashley, E. A., R. McGready, R. Hutagalung, L. Phaiphun, T. Slight, S. Proux, K. L. Thwai, M. Barends, S. Looareesuwan, N. J. White, and F. Nosten. 2005. A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria. Clin. Infect. Dis.41:425-432.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    Denis, M. B., T. M. Davis, S. Hewitt, S. Incardona, K. Nimol, T. Fandeur, Y. Poravuth, C. Lim, and D. Socheat. 2002. Efficacy and safety of dihydroartemisinin-piperaquine (Artekin) in Cambodian children and adults with uncomplicated falciparum malaria. Clin. Infect. Dis.35:1469-1476.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    Food and Drug Administration. 2003. Guidance for industry. Bioavailability and bioequivalence studies for orally administered drug products—general considerations. Food and Drug Administration, Washington, DC.
  5. 5.↵
    Gibaldi, M., and D. Perrier. 1982. Pharmacokinetics. Marcel Dekker Inc., New York, NY.
  6. 6.↵
    Hai, T. N., S. F. Hietala, N. Van Huong, and M. Ashton. 2008. The influence of food on the pharmacokinetics of piperaquine in healthy Vietnamese volunteers. Acta Trop.107:145-149.
    OpenUrlCrossRefPubMedWeb of Science
  7. 7.↵
    Hung, T. Y., T. M. Davis, K. F. Ilett, H. Karunajeewa, S. Hewitt, M. B. Denis, C. Lim, and D. Socheat. 2004. Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria. Br. J. Clin. Pharmacol.57:253-262.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    Karunajeewa, H. A., K. F. Ilett, I. Mueller, P. Siba, I. Law, M. Page-Sharp, E. Lin, J. Lammey, K. T. Batty, and T. M. Davis. 2008. Pharmacokinetics and efficacy of piperaquine and chloroquine in Melanesian children with uncomplicated malaria. Antimicrob. Agents Chemother.52:237-243.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    Le, N. H., K. Na-Bangchang, T. D. Le, K. A. Thrinh, and J. Karbwang. 1999. Pharmacokinetics of a single oral dose of dihydroartemisinin in Vietnamese healthy volunteers. Southeast Asian J. Trop. Med. Public Health30:11-16.
    OpenUrlPubMed
  10. 10.↵
    Lindegårdh, N., N. J. White, and N. P. Day. 2005. High throughput assay for the determination of piperaquine in plasma. J. Pharm. Biomed. Anal.39:601-605.
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    Na-Bangchang, K., S. Krudsood, U. Silachamroon, P. Molunto, O. Tasanor, K. Chalermrut, N. Tangpukdee, O. Matangkasombut, S. Kano, and S. Looareesuwan. 2004. The pharmacokinetics of oral dihydroartemisinin and artesunate in healthy Thai volunteers. Southeast Asian J. Trop. Med. Public Health35:575-582.
    OpenUrlPubMed
  12. 12.↵
    Nguyen, T. C., N. Q. Nguyen, X. T. Nguyen, D. Bui, T. Travers, and M. D. Edstein. 2008. Pharmacokinetics of the antimalarial drug piperaquine in healthy Vietnamese subjects. Am. J. Trop. Med. Hyg.79:620-623.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    Nosten, F., and N. J. White. 2007. Artemisinin-based combination treatment of falciparum malaria. Am. J. Trop. Med. Hyg.77:181-192.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    Ratcliff, A., H. Siswantoro, E. Kenangalem, R. Maristela, R. M. Wuwung, F. Laihad, E. P. Ebsworth, N. M. Anstey, E. Tjitra, and R. N. Price. 2007. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet369:757-765.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    Schuirmann, D. J. 1987. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J. Pharmacokinet. Biopharm.15:657-680.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    Sim, I. K., T. M. Davis, and K. F. Ilett. 2005. Effects of a high-fat meal on the relative oral bioavailability of piperaquine. Antimicrob. Agents Chemother.49:2407-2411.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    Tarning, J., E. A. Ashley, N. Lindegardh, K. Stepniewska, L. Phaiphun, N. P. Day, R. McGready, M. Ashton, F. Nosten, and N. J. White. 2008. Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinin-piperaquine in patients with Plasmodium falciparum malaria in Thailand. Antimicrob. Agents Chemother.52:1052-1061.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    Tarning, J., N. Lindegardh, A. Annerberg, T. Singtoroj, N. P. Day, M. Ashton, and N. J. White. 2005. Pitfalls in estimating piperaquine elimination. Antimicrob. Agents Chemother.49:5127-5128.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    White, N. J. 2006. Malaria—time to act. N. Engl. J. Med.355:1956-1957.
    OpenUrlCrossRefPubMed
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Pharmacokinetics and Bioequivalence Evaluation of Two Fixed-Dose Tablet Formulations of Dihydroartemisinin and Piperaquine in Vietnamese Subjects
Nguyen Trong Chinh, Nguyen Ngoc Quang, Nguyen Xuan Thanh, Bui Dai, Jason P. Geue, Russell S. Addison, Thomas Travers, Michael D. Edstein
Antimicrobial Agents and Chemotherapy Jan 2009, 53 (2) 828-831; DOI: 10.1128/AAC.00927-08

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Pharmacokinetics and Bioequivalence Evaluation of Two Fixed-Dose Tablet Formulations of Dihydroartemisinin and Piperaquine in Vietnamese Subjects
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Pharmacokinetics and Bioequivalence Evaluation of Two Fixed-Dose Tablet Formulations of Dihydroartemisinin and Piperaquine in Vietnamese Subjects
Nguyen Trong Chinh, Nguyen Ngoc Quang, Nguyen Xuan Thanh, Bui Dai, Jason P. Geue, Russell S. Addison, Thomas Travers, Michael D. Edstein
Antimicrobial Agents and Chemotherapy Jan 2009, 53 (2) 828-831; DOI: 10.1128/AAC.00927-08
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

antimalarials
artemisinins
quinolines

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596