Publications

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2015
Idowu, PA, Williams KO, Balogun JA, Oluwaranti AI.  2015.  Breast Cancer Risk Prediction Using Data Mining Classification Techniques. Transactions on Networks and Communications. 3(2):1-11.
Olagunju, A, Bolaji O, Amara A, Waitt C, Else L, Adejuyigbe E, Siccardi M, Back D, Khoo S, Owen A.  2015.  Breast milk pharmacokinetics of efavirenz and breastfed infants' exposure in genetically-defined subgroups of mother-infant pairs: an observational study. Clinical Infectious Diseases. AbstractWebsite

Background. The antiretroviral drug efavirenz is widely used during breastfeeding. Evaluating its safety requires an understanding of its breast milk pharmacokinetics, level of breastfed infants' exposure and potential influence of polymorphisms in drug disposition genes.

Methods. For this observational study, we investigated plasma and breast milk pharmacokinetics of efavirenz and breastfed infants' exposure in HIV positive nursing mothers and their breastfed infants. We also evaluated potential variability due to genetic polymorphisms in CYP2B6, NR1I3, CYP2A6, ABCB1, ABCB5 and ABCG2.

Results. CYP2B6 516G>T was independently associated with efavirenz concentrations in maternal plasma, breast milk and infant plasma (n=134). When stratified based on CYP2B6 516G>T (n=29 ; 11 GG, 10 GT and 8 TT), EFV pharmacokinetic parameters in plasma and breast milk differed significantly between patient groups. The median time averaged milk-to-plasma concentration ratio was 1.10 (range: 0.57-1.71). The estimated maximum infant efavirenz dose from breast milk was 809 µg/kg/day (215-2760) and paediatric dose weight-adjusted exposure index was 4.05% (1.08-13.8). Infant plasma concentrations did not change significantly during the dosing interval, 157 ng/mL (28.6-1360) in pooled analysis and 315 ng/mL (108-1360) in CYP2B6 516TT group. Infant plasma concentrations were highest up to 8 days of age at 1590 ng/mL (190-4631) and decreased by about 90% in the age stratum day 9 to 3 months. No efavirenz related toxicity was reported.

Conclusions. Most breastfed infants are exposed to less than 10% of the weight-adjusted therapeutic paediatric dose, the safety threshold for exposure to maternal drugs from breast milk.

Olagunju, A, Bolaji O, Amara A, Waitt C, Else L, Adejuyigbe E, Siccardi M, Back D, Khoo S, Owen A.  2015.  Breast milk pharmacokinetics of efavirenz and breastfed infants’ exposure in genetically-defined subgroups of mother-infant pairs: an observational study. Clinical Infectious Diseases. 61(3):453-63. Abstract

BACKGROUND: The antiretroviral drug efavirenz is widely used during breastfeeding. Evaluating its safety requires an understanding of its breast milk pharmacokinetics, level of breastfed infants' exposure, and potential influence of polymorphisms in drug disposition genes.

METHODS: For this observational study, we investigated plasma and breast milk pharmacokinetics of efavirenz and breastfed infants' exposure in human immunodeficiency virus positive nursing mothers and their breastfed infants. We also evaluated potential variability due to genetic polymorphisms in CYP2B6, NR1I3, CYP2A6, ABCB1, ABCB5, and ABCG2.

RESULTS: CYP2B6 516G>T was independently associated with efavirenz concentrations in maternal plasma, breast milk, and infant plasma (n = 134). When stratified based on CYP2B6 516G>T (n = 29 ; 11 GG, 10 GT and 8 TT), efavirenz pharmacokinetic parameters in plasma and breast milk differed significantly between patient groups. The median time-averaged milk-to-plasma concentration ratio was 1.10 (range: 0.57-1.71). The estimated maximum infant efavirenz dose from breast milk was 809 µg/kg/day (215-2760) and pediatric dose weight-adjusted exposure index was 4.05% (1.08-13.8). Infant plasma concentrations did not change significantly during the dosing interval, 157 ng/mL (28.6-1360) in pooled analysis and 315 ng/mL (108-1360) in CYP2B6 516TT group. Infant plasma concentrations were highest up to 8 days of age at 1590 ng/mL (190-4631) and decreased by about 90% in the age stratum day 9 to 3 months. No efavirenz related toxicity was reported.

CONCLUSIONS: Most breastfed infants are exposed to <10% of the weight-adjusted therapeutic pediatric dose, the safety threshold for exposure to maternal drugs from breast milk.

Owoade, OK, Hopke PK, Olise FS, Ogundele LT, Fawole OG, Olaniyi HB, Jegede OO, Ayoola M, Bashiru MI.  2015.  Chemical compositions and source identification of particulate matter (PM2.5 and PM2.5–10) from a scrap iron and steel smelting industry along the Ife–Ibadan highway, Nigeria. Atmospheric Pollution Research. 6:107-119.
Falade, DA, Adeyemi BA.  2015.  Civic Education in Nigeria's One Hundred Year of Existence: Problems & Prospects. Journal of Emerging Trends in Educational Research and Policy Studies. 6(1):113-118.
Siccardi, M, Olagunju A, Simiele M, D'Avolio A, Calcagno A, Bonora S, Perri DG, Owen A.  2015.  Classspecific relative genetic contribution for key antiretroviral drugs. Journal of Antimicrobial Chemotherapy. 70(11):3074-9. Abstract

OBJECTIVES: Antiretroviral pharmacokinetics is defined by numerous factors affecting absorption, distribution, metabolism and elimination. Biological processes underpinning drug distribution are only partially characterized and multiple genetic factors generate cumulative or antagonistic interactions, which complicates the implementation of pharmacogenetic markers. The aim of this study was to assess the degree to which heredity influences pharmacokinetics through the quantification of the relative genetic contribution (rGC) for key antiretrovirals.

METHODS: A total of 407 patients receiving lopinavir/ritonavir, atazanavir/ritonavir, atazanavir, efavirenz, nevirapine, etravirine, maraviroc, tenofovir or raltegravir were included. Intra-patient variability (SDw) and inter-patient (SDb) variability were measured in patients with plasma concentrations available from more than two visits. The rGC was calculated using the following equation: 1 - (1 / F) where F = SDb(2) / SDw(2).

RESULTS: Mean (95% CI) rGC was calculated to be 0.81 (0.72-0.88) for efavirenz, 0.74 (0.61-0.84) for nevirapine, 0.67 (0.49-0.78) for etravirine, 0.65 (0.41-0.79) for tenofovir, 0.59 (0.38-0.74) for atazanavir, 0.47 (0.27-0.60) for atazanavir/ritonavir, 0.36 (0.01-0.48) for maraviroc, 0.15 (0.01-0.44) for lopinavir/ritonavir and 0 (0-0.33) for raltegravir.

CONCLUSIONS: The rank order for genetic contribution to variability in plasma concentrations for the study drugs was efavirenz > nevirapine > etravirine > tenofovir > atazanavir > atazanavir/ritonavir > maraviroc > lopinavir/ritonavir > raltegravir, indicating that class-specific differences exist. The rGC strategy represents a useful tool to rationalize future investigations as drugs with higher rGC scores may represent better candidates for pharmacogenetic-pharmacokinetic studies.

Oladokun, TT, ODEBODE AA.  2015.  Collaborative Practice in the Procurement of Valuation Services in Lagos State, Nigeria. Journal Of Environmental Design and Management. 7(2):4-12.
Oyebola, OO, Ogungbemi KI, Olopade MA.  2015.  COMPARISON OF THE EMISSION PROPERTIES OF Ho :KPb Cl AND Ho :CaF 2 5 2 CRYSTALS. Ife Journal of Science. 17(2)
Fawole, OG, Olofinjana B, Owoade OK.  2015.  Compositional and Air-mass Trajectory Analysis of a Heavy Dust Episode (HDE) Aerosols in Ile-Ife, Nigeria. British Journal of Applied Science & Technology. 13(1):1-15.bjast_hde_paper.pdf
ADESOLA, F.  2015.  Congo DR and the Intrigues of Resource-Based Conflict. African Research Review. Vol. 9(1, S/No. 36):62-72.
Ogunwande, GA, Akinola EO, Lana AR.  2015.  DEVELOPMENT OF A BIOGAS-POWERED POULTRY EGG INCUBATOR. Ife Journal of Science. 17(1)ogunwande_et_al_20.pdf
Idowu, PA, Ajibola SO, jeremiah Balogun A, Ogunlade O.  2015.  Development of a Fuzzy Logic Based Model for Monitoring Cardiovascular Disease Risk. Journal of Health Information Systems and Informatics. 10(4):38-55.
Olagunju, A, Bolaji OO, Amara A, Waitt C, Else L, Soyinka J, Adeagbo B, Adejuyigbe E, Siccardi M, Back D, Owen A, Khoo S.  2015.  Development, validation and clinical application of a novel method for the quantification of efavirenz in dried breast milk spots using LC-MS/MS. Journal of Antimicrobial Chemotherapy. 70(2):555-61. AbstractWebsite

Objectives This manuscript describes the development, validation and clinical application of a novel method for the quantification of the antiretroviral drug efavirenz in dried breast milk spots using LC-MS.

Methods Dried breast milk spots were prepared by spotting 30 μL of human breast milk on each circle of Whatman 903 Protein Saver cards. Chromatographic separation was achieved on a reverse-phase C18 column with 1 mM ammonium acetate in water/acetonitrile using a solvent gradient at a flow rate of 400 μL/min and detection was by TSQ Quantum Access triple quadrupole mass spectrometer equipped with a heated electrospray ionization source. The method was applied to characterize the breast milk pharmacokinetic profile of efavirenz in HIV-positive nursing mothers receiving regimens containing 600 mg of efavirenz once daily.

Results The assay was validated over the concentration range 50–7500 ng/mL. Accuracy ranged between 95.2% and 102.5% and precision ranged between 1.05% and 9.53%. The average recovery of efavirenz from dried breast milk spots was 106.4% and the matrix effect was 8.14%. Stability of efavirenz in dried breast milk spots and processed samples at room temperature, −40°C and −80°C was demonstrated. In the pharmacokinetic study, the mean (SD) AUC0–24, Cmax and Cmin of efavirenz in breast milk were 59 620 ng·h/mL (17 440), 4527 ng/mL (1767) and 1261 ng/mL (755.9), respectively. The mean (range) milk-to-plasma concentration ratio over the dosing interval was 0.78 (0.57–1.26).

Conclusions The dried breast milk spot method is simple, robust, accurate and precise, and can be used in settings with limited resources.