The EDCTP Alumni Network

Professor
Collen Masimirembwa

Related fellows

Associate Professor Yaya Kassogue

Associate professor in Genetic and Molecular Pathology

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Dr Zivai Nenguke

Project Director

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Ms Emily Awuor Abuonji

RESEARCH ASSISTANT

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Profile EDCTP Fellowship 1 EDCTP Fellowship 2

Project Title

A prospective study to evaluate a pharmacogenetic-guided dosing algorithm based on patient CYP2B6 genotype compared to the empirical standard dose in the safe and efficacious use of efavirenz in HIV/AIDS patients in Zimbabwe

EDCTP Project

TA.2011.40200.052

EDCTP Program

EDCTP1

EDCTP Project Call

Senior Fellowship (SF)

Project Objectives

Primary Objectives: 1. To compare efavirenz exposure levels in patients in whom the initiation dose is based on a pharmacogenetic algorithm with those in patients given the standard dose 2. To compare HIV viral load suppression and CD4 counts in patients in whom efavirenz dose is based on a pharmacogenetic algorithm with those in patients given the standard dose 3. To compare the incidences and severity of efavirenz associated adverse drug reactions; liver function, skin hypersensitivity reactions and central nervous system (CNS) effects in patients in whom the efavirenz dose is based on a pharmacogenetic algorithm with those given the standard dose 4. To validate the CYP2D6 genotyping method for use in the clinical study

Study Design

Prospective randomised controlled trial

Host Organisation

Department	Institution	Country
	African Institute of Biomedical Science and Technology (AiBST)	Zimbabwe

Sites

Wilkins Infectious Disease Hospital (Harare) Chitugwiza Hospital, Opportunistic Infections Unit (Chitugwiza)

Results & Outcomes

HIV/AIDS and TB cohort in Zimbabwe. We have conclusively shown that the CYP2B6*6 genotype is predictive of high concentrations of Project Porftolio Page 333 of 622 efavirenz and predisposition to CNS sides effects and require only 200 mg of the drug instead of the standard 600 mg a day. We have also shown that for the other patients heterozygous, that those carrying one defect CYP2B6 allele and those without a defect should only be given 400 mg of efavirenz a day. Our findings are supported by a recent major study, ENCORE, which demonstrated the non-inferiority of 400 mg to the 600 mg efavirenz dose. This therefore represents the climax of our study which medicines control regulatory authorities should now consider towards revising the use of this drug. We have now engaged the Medicines Control Authority of Zimbabwe (MCAZ) and the National AIDS Council (NAC). We have also been on radio stations explaining our results to the public, an outreach that has been well received and patients phoned in expressing their appreciation of having the reason for their ADRs explained based on our study. The work has also resulted in secondary of achievements such as: (1) Establishment of a Clinical Trial Research Group whose purpose is to critically discuss the design and execution of clinical studies in African settings. (2) Four publications (3) Initiation of a Clinical Trial Unit (CTC) at one of the major hospitals in Zimbabwe, Chitungwiza General Hospital, for the conduct of Phase I Clinical Studies. (4) The completion of PhD studies and successful defence of the thesis in December 2014, by Milcah Dhoro on Pharmacogenetics of Efavirenz

Project Title

Pharmacogenomics Research And Clinical Excellence in the Treatment of Infectious Diseases in African

EDCTP Project

TMA2016SF1508

EDCTP Program

EDCTP2

EDCTP Project Call

Senior Fellowship (SF)

Host Organisation

Department	Institution	Country
	African Institute of Biomedical Science & Technology (AIBST)	Zimbabwe

Sites

Wilkins Infectious Disease Hospital (Harare)

Current Organisation

African Institute of Biomedical Science and Technology (AIBST)

Current Job Title

Chief Scientific Officer

Biography

Publications

Authors:

L Afzelius, I Zamora, M Ridderström, TB Andersson, A Karlén, CM Masimirembwa

Journal:

Molecular pharmacology 59 (4)

Content:

Date:

2009-05-05

Authors:

Maimbo M, Kiyotani K, Mushiroda T, Masimirembwa C, Nakamura Y.

Journal:

Eur J Clin Pharmacol. 2012 Mar;68(3):267-71.

Content:

Date:

2012-03-06

Authors:

CM Masimirembwa, R Thompson, TB Andersson

Journal:

Combinatorial chemistry & high throughput screening 4 (3)

Content:

Date:

2001-05-05

Authors:

CM Masimirembwa C Otter M Berg M Jönsson B Leidvik E Jonsson TB Andersson.

Journal:

Content:

Date:

1999-01-01

Authors:

Hayeshi R, Masimirembwa C, Mukanganyama S, Ungell AL

Journal:

Biopharm Drug Dispos. 2008 Sep;29(6):324-34.

Content:

Date:

2008-09-29

Authors:

Kjellander B, Masimirembwa CM, Zamora I.

Journal:

J Chem Inf Model. 2007 May-Jun;47(3):1234-47

Content:

Date:

2007-05-31

Authors:

Adzu B, Mustapha KB, Masimirembwa C, Obodozie O, Kirim RA, Gamaniel KS. Avicenna J Phytomed

Journal:

2013 Summer;3(3):201-

Content:

Date:

2013-03-03

Authors:

XQ Li, A Björkman, TB Andersson, LL Gustafsson, CM Masimirembwa

Journal:

European journal of clinical pharmacology 59 (5-6

Content:

Date:

1996-05-05

Authors:

Dandara C, Huzair F, Borda-Rodriguez A, Chirikure S, Okpechi I, Warnich L, Masimirembwa C

Journal:

OMICS. 2014 Dec;18(12):733-9

Content:

Date:

2014-12-18

Authors:

Gutierrez MM, Pillai G, Felix S, Romero F, Onyango KO, Owusu-Agyei S, Asante KP, Barnes KI, Sinxadi P, Allen E, Abdulla S, Masimirembwa C, Munyoro M, Yimer G, Gebre-Mariam T, Spector J, Ogutu B

Journal:

Clin Pharmacol Ther; 10.1002/cpt.695. [Epub ahead of print]

Content:

Date:

2017-04-05

Authors:

TE Bapiro, AC Egnell, JA Hasler, CM Masimirembwa

Journal:

Drug Metabolism and disposition 29 (1),

Content:

Date:

2001-05-05

Authors:

C Nyakutira D Röshammar E Chigutsa P Chonzi M Ashton C Nhachi CM Masimirembwa

Journal:

Content:

Date:

2008-01-01

Authors:

Chimukangara B, Gwanzura L, Mitchell R, Katzenstein D, Masimirembwa C

Journal:

Curr HIV Res. 2014;12(5):309-16

Content:

Date:

2014-12-05

Authors:

Thelingwani RS, Zvada SP, Dolgos H, Ungell AL, Masimirembwa CM

Journal:

Drug Metab Dispos. 2009 Jun;37(6):1286-94

Content:

Date:

2009-06-03

Authors:

Matimba A, Tybring G, Chitereka J, Zinyama-Gutsire R, Dandara C, Bürén E, Dhoro M, Masimirembwa C

Journal:

Biopreserv Biobank. 2016 Apr 15. [Epub ahead of print] PMID: 27082894

Content:

Date:

2016-04-15

Authors:

Grobler L, Grobler A, Haynes R, Masimirembwa C. Thelingwani R, Steenkamp P, Steyn HS

Journal:

Expert Opin Drug Metab Toxicol. 2014 Mar;10(3):313-25

Content:

Date:

2014-03-24

Authors:

CM Masimirembwa C Otter M Berg M Jönsson B Leidvik E Jonsson

Journal:

Content:

Date:

1999-01-01

Authors:

Adzu B, Masimirembwa C, Mustapha KB, Thelingwani R, Kirim RA, Gamaniel KS

Journal:

Eur J Drug Metab Pharmacokinet. 2015 Mar;40(1):115-8.

Content:

Date:

2015-03-04

Authors:

Bonn B, Masimirembwa CM, Castagnoli N Jr

Journal:

Drug Metab Dispos. 2010 Jan;38(1):187-99.

Content:

Date:

2010-01-04

Authors:

CM Masimirembwa, C Otter, M Berg, M Jönsson, B Leidvik, E Jonsson, ...

Journal:

Drug Metabolism and Disposition 27 (10),

Content:

Date:

1999-05-05

Authors:

Manasa J, Musabaike H, Masimirembwa C, Burke E, Luthy R, Mudzori J

Journal:

Clin Vaccine Immunol. 2007 Mar;14(3):293-8.

Content:

Date:

2007-03-14

Authors:

Simms V, Dauya E, Dakshina S, Bandason T, McHugh G, Munyati S, Chonzi P, Kranzer K, Ncube G, Masimirembwa C, Thelingwani R, Apollo T, Hayes R, Weiss HA, Ferrand RA. PLoS Med

Journal:

e1002360. doi: 10.1371/journal.pmed.1002360. eCollection

Content:

Date:

2018-07-25

Authors:

Adigun RA, Martincigh B, Nyamori VO, Omondi B, Masimirembwa C, Simoyi RH.

Journal:

Dalton Trans. 2014 Sep 14;43(34):12943-51

Content:

Date:

2014-09-14

Authors:

Johansson T, Jurva U, Grönberg G, Weidolf L, Masimirembwa C

Journal:

Drug Metab Dispos. 2009 Mar;37(3):571-9.

Content:

Date:

2009-03-03

Authors:

Jurva U, Holmén A, Grönberg G, Masimirembwa C, Weidolf L

Journal:

Chem Res Toxicol. 2008 Apr;21(4):928-35.

Content:

Date:

2008-04-21

Authors:

Dhoro M, Ngara B, Kadzirange G, Nhachi C, Masimirembwa C

Journal:

Curr HIV Res. 2013 Sep;11(6):481-90.

Content:

Date:

2013-09-11

Authors:

Thelingwani R, Masimirembwa C.

Journal:

Curr Drug Metab. 2014;15(10):942-52

Content:

Date:

2014-10-10

Authors:

Zawaira A, Matimba A, Masimirembwa C

Journal:

Pharmacogenet Genomics. 2008 Jun;18(6):467-76

Content:

Date:

2008-06-18

Authors:

CM Masimirembwa, C Otter, M Berg, M Jönsson, B Leidvik, E Jonsson, TB Andersson

Journal:

Drug Metabolism and Disposition 27 (10)

Content:

Date:

1999-05-05

Authors:

Ongarora DS, Strydom N, Wicht K, Njoroge M, Wiesner L, Egan TJ, Wittlin S, Jurva U, Masimirembwa CM, Chibale K.

Journal:

Bioorg Med Chem. 2015 Sep 1;23(17):5419-32.

Content:

Date:

2015-09-01

Authors:

XQ Li A Björkman TB Andersson LL Gustafsson CM Masimirembwa

Journal:

Content:

Date:

2003-01-01

Authors:

7. Rhead R, Masimirembwa C, Cooke G, Takaruza A, Nyamukapa C, Mutsimhi C, Gregson S

Journal:

PLoS One. 2016 Dec 14;11(12):e0167852. doi: 10.1371/journal.pone.0167852. eCollection 2016.

Content:

Date:

2016-12-14

Authors:

Dhoro M, Zvada S, Ngara B, Nhachi C, Kadzirange G, Chonzi P, Masimirembwa C.

Journal:

BMC Pharmacol Toxicol. 2015 Mar 27;16:4.

Content:

Date:

2015-03-27

Authors:

XQ Li, A Björkman, TB Andersson, M Ridderström, CM Masimirembwa

Journal:

Pharmacology and Experimental Therapeutics 300 (2)

Content:

Amodiaquine (AQ) metabolism to N-desethylamodiaquine (DEAQ) is the principal route of disposition in humans. Using human liver microsomes and two sets of recombinant human cytochrome P450 isoforms (from lymphoblastoids and yeast) we performed studies to identify the CYP isoform(s) involved in the metabolism of AQ. CYP2C8 was the main hepatic isoform that cleared AQ and catalyzed the formation of DEAQ. The extrahepatic P450s, 1A1 and 1B1, also cleared AQ and catalyzed the formation of an unknown metabolite M2. TheK_m and V_maxvalues for AQ N-desethylation were 1.2 μM and 2.6 pmol/min/pmol of CYP2C8 for recombinant CYP2C8, and 2.4 μM and 1462 pmol/min/mg of protein for human liver microsomes (HLMs), respectively. Relative contribution of CYP2C8 in the formation of DEAQ was estimated at 100% using the relative activity factor method. Correlation analyses between AQ metabolism and the activities of eight hepatic P450s were made on 10 different HLM samples. Both the formation of DEAQ and the clearance of AQ showed excellent correlations (r² = 0.98 and 0.95) with 6α-hydroxylation of paclitaxel, a marker substrate for CYP2C8. The inhibition of DEAQ formation by quercetin was competitive withK_i values of 1.96 for CYP2C8 and 1.56 μM for HLMs. Docking of AQ into the active site homology models of the CYP2C isoforms showed favorable interactions with CYP2C8, which supported the likelihood of an N-desethylation reaction. These data show that CYP2C8 is the main hepatic isoform responsible for the metabolism of AQ. The specificity, high affinity, and high turnover make AQ desethylation an excellent marker reaction for CYP2C8 activity.

Date:

2002-01-02

Authors:

Matimba A, Oluka MN, Ebeshi BU, Sayi J, Bolaji OO, Guantai AN, Masimirembwa CM

Journal:

Eur J Hum Genet. 2008 Jul;16(7):780-3.

Content:

Date:

2008-07-08

Authors:

Ericsson T, Masimirembwa C, Abelo A, Ashton M

Journal:

Drug Metab Lett. 2012;6(4):247-57

Content:

Date:

2012-04-02

Authors:

Afzelius L, Raubacher F, Karlén A, Jørgensen FS, Andersson TB, Masimirembwa CM, Zamora I

Journal:

Drug Metab Dispos. 2004 Nov;32(11):1218-29.

Content:

Date:

2004-11-11

Authors:

Thelingwani R, Bonn B, Chibale K, Masimirembwa C

Journal:

Expert Opin Drug Metab Toxicol. 2014 Oct;10(10):1313-24.

Content:

Date:

2014-10-10

Authors:

Makadzange AT, Higgins-Biddle M, Chimukangara B, Birri R, Gordon M, Mahlanza T, McHugh G, van Dijk JH, Bwakura-Dangarembizi M, Ndung'u T, Masimirembwa C, Phelps B, Amzel A, Ojikutu BO, Walker BD, Ndhlovu CE

Journal:

PLoS One. 2015 Dec 14;10(12):

Content:

Date:

2015-12-14

Authors:

Njuguna NM, Masimirembwa C, Chibale K

Journal:

J Nat Prod. 2012 Mar 23;75(3):507-13.

Content:

Date:

2012-03-23

Authors:

L Afzelius I Zamora M Ridderström TB Andersson A Karlén CM Masimirembwa

Journal:

Content:

Date:

2001-01-01

Authors:

CM Masimirembwa, U Bredberg, TB Andersson

Journal:

Clinical pharmacokinetics 42 (6),

Content:

Date:

2003-05-05

Authors:

4. Makadzange AT, Boyd FK, Chimukangara B, Masimirembwa C, Katzenstein D, Ndhlovu CE

Journal:

J Clin Microbiol. 2017 Jul;55(7):2172-2179. doi: 10.1128/JCM.00176-17

Content:

Date:

2017-05-03

Authors:

Chimukangara B, Manasa J, Mitchell R, Nyabadza G, Katzenstein D, Masimirembwa C

Journal:

AIDS Res Hum Retroviruses

Content:

Date:

2016-10-26

Authors:

CM Masimirembwa U Bredberg TB Andersson

Journal:

Content:

Date:

2003-01-01

Authors:

Ongarora DS, Gut J, Rosenthal PJ, Masimirembwa CM, Chibale K

Journal:

Bioorg Med Chem Lett. 2012 Aug 1;22(15):5046-5010.

Content:

Date:

2012-08-01

Authors:

Bonn B, Masimirembwa CM, Aristei Y, Zamora I

Journal:

Drug Metab Dispos. 2008 Nov;36(11):2199-210

Content:

Date:

1998-11-02

Authors:

Cotton RG; 2006 Human Variome Project, Appelbe W, Auerbach AD, Becker K, Bodmer W, Boone DJ, Boulyjenkov V, Brahmachari S, Brody L, Brookes A, Brown AF, Byers P, Cantu JM, Cassiman JJ, Claustres M, Concannon P, Cotton RG, den Dunnen JT, Flicek P, Gibbs R, Hall J, Hasler J, Katz M, Kwok PY, Laradi S, Lindblom A, Maglott D, Marsh S, Masimirembwa CM, Minoshima S, de Ramirez AM, Pagon R, Ramesar R, Ravine D, Richards S, Rimoin D, Ring HZ, Scriver CR, Sherry S, Shimizu N, Stein L, Tadmouri GO, Taylor G, Watson M

Journal:

Nat Genet. 2007 Apr;39(4):433-6.

Content:

Date:

2007-04-03

Authors:

Thelingwani RS, Dhansay K, Smith P, Chibale K, Masimirembwa CM

Journal:

Xenobiotica. 2012 Oct;42(10):989-1000.

Content:

Date:

2012-10-12

Authors:

Soko ND, Masimirembwa C, Dandara C. OMICS.

Journal:

2016 Sep;20(9):498-509. doi: 10.1089/omi.2016.0114.PMID: 27631189

Content:

Date:

2016-09-20

Authors:

Matimba A, Del-Favero J, Van Broeckhoven C, Masimirembwa C

Journal:

Hum Genomics. 2009 Jan;3(2):169-90.

Content:

Date:

2009-01-05

Authors:

Afzelius L, Zamora I, Masimirembwa CM, Karlén A, Andersson TB, Mecucci S, Baroni M, Cruciani G.

Journal:

J Med Chem. 2004 Feb 12;47(4):907-14.

Content:

Date:

2004-02-12

Authors:

Thelingwani R, Leandersson C, Bonn B, Smith P, Chibale K, Masimirembwa C

Journal:

Xenobiotica. 2015 Sep 4:1-7. [Epub ahead of print] PMID: 26338168

Content:

Date:

2015-09-04

Authors:

1. Soko ND, Masimirembwa C, Dandara C

Journal:

BMC Res Notes.

Content:

Date:

2019-06-14

Authors:

Jurva U, Holmén A, Grönberg G, Masimirembwa C, Weidolf L

Journal:

Chem Res Toxicol. 2008 Apr;21(4):928-35.

Content:

Date:

2008-04-21

Authors:

Bapiro TE, Sayi J, Hasler JA, Jande M, Rimoy G, Masselle A, Masimirembwa CM

Journal:

Eur J Clin Pharmacol. 2005 Nov;61(10):755-61.

Content:

Date:

2005-11-07

Authors:

Adeagbo BA, Bolaji OO, Olugbade TA, Durosinmi MA, Bolarinwa RA, Masimirembwa C. J Clin

Journal:

Pharm Ther. 2016 Oct;41(5):546-51. doi: 10.1111/jcpt.12424. PMID: 27426203

Content:

Date:

2016-10-14

Authors:

Chigorimbo-Murefu NT, Njoroge M, Nzila A, Louw S, Masimirembwa C, Chibale K

Journal:

Future Med Chem. 2012 Dec;4(18):2325-36.

Content:

Date:

2012-12-04

Authors:

Chibale K, Guantai EM, Masimirembwa C.

Journal:

Future Med Chem. 2011 Mar;3(3):257-61

Content:

Date:

2011-03-03

Authors:

XQ Li A Björkman TB Andersson M Ridderström CM Masimirembwa.

Journal:

Content:

Date:

2002-01-01

Authors:

Hayeshi R, Masimirembwa C, Mukanganyama S, Ungell AL

Journal:

Eur J Pharm Sci. 2006 Sep;29(1):70-81.

Content:

Date:

2006-09-29

Authors:

Masimirembwa C, Dandara C, Leutscher PD

Journal:

OMICS. 2016 Oct;20(10):575-580. PMID: 27627692

Content:

Date:

2016-10-20

Authors:

Dandara C, Swart M, Mpeta B, Wonkam A, Masimirembwa C

Journal:

Expert Opin Drug Metab Toxicol. 2014 Jun;10(6):769-85.

Content:

Date:

2014-06-10

Authors:

Nyakutira C, Röshammar D, Chigutsa E, Chonzi P, Ashton M, Nhachi C, Masimirembwa C. Eur J

Journal:

Clin Pharmacol. 2008 Apr;64(4):357-65.

Content:

Date:

2008-04-07

Authors:

Persson KP, Ekehed S, Otter C, Lutz ES, McPheat J, Masimirembwa CM, Andersson TB

Journal:

Pharm Res. 2006 Jan;23(1):56-69

Content:

Date:

2006-01-23

Authors:

Dhoro M, Nhachi C , Masimirembwa C.

Journal:

African Journal of Biotechnology

Content:

Date:

2013-01-01

Authors:

C MASIMIREMBWA I PERSSON L BERTILSSON J HASLER

Journal:

Content:

Date:

1996-01-01

Authors:

TE Bapiro AC Egnell JA Hasler CM Masimirembwa

Journal:

Content:

Date:

2001-01-01

Authors:

Awortwe C, Bouic PJ, Masimirembwa CM, Rosenkranz B

Journal:

Drug Metab Lett. 2014 Jul;7(2):83-95.

Content:

Date:

2014-07-07

Authors:

C Nyakutira, D Röshammar, E Chigutsa, P Chonzi, M Ashton, C Nhachi, CM Masimirembwa

Journal:

European journal of clinical pharmacology 64 (4)

Content:

Date:

2008-05-05

Authors:

C MASIMIREMBWA, I PERSSON, L BERTILSSON, J HASLER

Journal:

British journal of clinical pharmacology 42 (6)

Content:

Date:

2009-05-05

Authors:

CM Masimirembwa R Thompson TB Andersson

Journal:

Content:

Date:

2001-01-01

Authors:

Mao M, Matimba A, Scordo MG, Gunes A, Zengil H, Yasui-Furukori N, Masimirembwa C, Dahl ML

Journal:

Pharmacogenomics. 2009 Sep;10(9):1447-55.

Content:

Date:

2009-09-10

Professor Collen Masimirembwa

Related fellows

Associate Professor Yaya Kassogue

Dr Zivai Nenguke

Ms Emily Awuor Abuonji

Project Title

EDCTP Project

EDCTP Program

EDCTP Project Call

Project Objectives

Study Design

Host Organisation

Sites

Results & Outcomes

Project Title

EDCTP Project

EDCTP Program

EDCTP Project Call

Host Organisation

Sites

Current Organisation

Current Job Title

Biography

Publications

Professor
Collen Masimirembwa