Faculty of Pharmacy
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- ItemOpen AccessPatient's adherence to antiretroviral therapy in Lagos State University Teaching Hospital (LASUTH), Ikeja, Lagos, Nigeria(School of Postgraduate Studies of the University of Lagos, Akoka, 2013-02) Aderemi-Williams, R.I.Evidence abound that successful management of HIV and AIDS using Highly Active Antiretroviral Therapy (HAART) requires not less than 95% adherence. Longitudinal studies measuring adherence using four different tools have not been documented in Africa. The use of different tools to determine and predict factors that may affect adherence in Nigeria has not been documented to the best of our knowledge. A study (comprising of 3-month retrospective and 45-month prospective) was carried out in Lagos State University Teaching Hospital (LASUTH) between December, 2006 to December, 2010. Validated questionnaires and monitoring of patients’ clinical progress were used. Adherence was assessed using self-report, unannounced pill counts, doctor’s appointment attendance, and pharmacy refill record. Patients with 95% and above adherence levels were considered adherent. Data collected from 248 of the 294 (84.35%) patients eligible for the study were analysed. ANOVA was used to compare and determine the adequacy of the adherence assessment tools. Predictors of adherence were determined with logistic regression models and paired sample t-test was used to test effect on patients’ CD4 count. Social and clinical demographic data analysis of study patients show that 134 (54.00%) were married, 58 (23.40%) were single; 148 (59.70%) females, 100 (40.30%) males; 211 (85.10%) were Christians, 31 (12.50%) were Muslims; 106 (42.70%) had secondary school education, 67 (27.00%) had tertiary education, 43 (17.3%) had primary education and 139 (56.05%) were employed. Their mean age was 40.39 ±8.78 years and mean baseline CD4 cell count was 143.46 ±92.72 cell/μL. At baseline, 66.10% of the patients were on 12- hourly regimen while 33.90% were on 24-hourly regimen. XXX Unannounced pill count (mean = 96.97±6.02) measure was found to be the best measure for patient’s adherence, followed by pharmacy refill (mean = 96.64±6.95), self-report (mean = 95.26±15.51) and doctor’s appointment attendance (mean = 74.70±14.93) measure. None of the variables studied was a predictor of adherence using self-report as a measure of adherence. Using unannounced pill counts: younger age (18-39 years), being Muslim and patients’ knowledge of transmission were predictors of adherence. In doctor’s appointment attendance measure of adherence; knowledge of management, knowledge of adherence, knowledge of HIV pathogenesis and patients’ habits predicted adherence. The following are predictors of adherence when measured with pharmacy refill record: marital status, Muslim religion, tertiary education, being a professional, skilled worker, knowledge of drug management, knowledge of adherence and presence of social support. The effect of highly active antiretroviral therapy (HAART) on improving the immunological status of patients was significant. Adherence was dynamic over the study period. The study was also able to identify many possible predictors of adherence with pharmacy refill record identifying most predictors. Due to identified gaps in patients’ CD4 count monitoring, the difference in immunological status between adherent and non-adherent patients was not significant
- ItemOpen AccessStudies on the rational use of chloroquine in the management of uncomplicated malaria in Lagos State General Hospitals(School of Postgraduate Studies of the University of Lagos, Akoka, 2005-11) Aina, B.A.Malaria is a curable and preventable disease and it is a major public health problem in Nigeria and Chloroquine is still the first line drug in its treatment in Nigeria. Inappropriate prescribing which is the failure to prescribe drugs in accordance with guidelines based on scientific evidence to ensure safe, effective, and economic use, is an irrational drug use behavior. Increased benefits from chloroquine or a slow down of progression to resistance could be achieved by improving prescribing practice, drug quality, and patient compliance. The objectives of the study were to determine the impact of two modes of educational intervention on chloroquine prescribing pattern of prescribers in Lagos State General Hospitals, to determine the quality of chloroquine dosage forms available in these hospitals and to undertake cost effectiveness analysis of chloroquine tablet and injection. The study was carried out in all the ten General Hospitals under Lagos State Hospitals Management Board. One hundred prescriptions each for adults and children at each hospital were systematically sampled between January and December 2000. Where there were fewer than 100 prescriptions all the prescriptions available were sampled for quantitative analysis. Questionnaires were distributed to prescribers between November and December 2001 for quantitative and qualitative analysis. Quality of the chloroquine dosage forms available in these hospitals was determined using British Pharmacopoeiea methods. The cost effectiveness analysis of chloroquine tablet and injection chloroquine was calculated Educational intervention took place between January and February 2002. Seminars were presented in 8 out of the 10 hospitals. Among the 8 that had seminars, 4 hospitals had xvi educational posters while the other 4 had plastic boxes describing correct doses of chloroquine left behind. Two hospitals served as control. There was significant increase in the percentage of prescriptions with correct dosage of chloroquine post-intervention compared with pre-intervention (p< 0.01). There was association between intervention and correctness of dosage of chloroquine prescribed (p<0.001). There was association between the mode of intervention and dosage of chloroquine prescribed (p<0.001). There was also association between the dosage of chloroquine and the different dosage forms of chloroquine prescribed (p<0.001). There was no significant difference between the group with plastic box and the group with poster in percentage of correct prescriptions (p>0.05). There was no statistically significant difference in percentage of correct prescriptions between 1 month, 3 months, 6 months and 12 months post intervention hence outcome of intervention was sustained. The tablets passed the quality tests more than the two other dosage forms. Tablet chloroquine was more cost effective than injection chloroquine The conclusion from this study is that educational intervention improved the prescribing pattern of chloroquine. Tablet should be encouraged more than injection because it is safer and more cost effective. There is need to determine the quality of chloroquine available in our hospitals.
- ItemOpen AccessAntimalarial resistance genes polymorphism and imunoendocrine biomarker profile in patients with uncomplicated plasmodium falciparum malaria in Lagos, Nigeria(School of Postgraduate Studies of the University of Lagos, Akoka, 2020-01) Idowu, A.O.The threat of a possible emergence of resistance to currently recommended artemisinin based combination therapies (ACTs) against malaria, has made proactive surveillance for resistance markers imperative for early detection of resistance before they become widespread. The changing pattern of malaria transmission due to reduction in cases has also made reassessment of cytokine and endocrine response in malaria infection important. This study assessed antimalarial resistance genes polymorphism and immunoendocrine biomarker profile in patients with uncomplicated Plasmodium falciparum malaria in Lagos, Nigeria. Blood samples collected between July, 2015 and August, 2016 in 3 health facilities in Lagos from a cross section of 2,534 consenting patients with symptoms consistent with malaria were screened for P. falciparum by microscopy and RDT. Thirty-seven samples positive for P. falciparum from patients with self- reported antimalarial medication use were selected for molecular studies. Genomic DNA of malaria positive samples were extracted from dried blood spots (DBS) using QIAamp DNA mini-kit (Qiagen, Valencia, CA). Sanger and next generation sequencing (NGS) methods were used to screen for mutations in three genes (Pfcrt, Pfmdr1 and Pfk13) that have been previously associated with antimalarial resistance. Amplification and sequencing of the Pfk13, Pfcrt, and Pfmdr1 genes was successfully performed in 26 samples. Plasma concentration for cytokines (IL-12p70, IFN-γ, TNF-α, IL-10, TGF-β), and corticosteroids (cortisol and dexamethasone) were evaluated using enzyme-linked immunosorbent assay (ELISA) in twenty-six patients’ samples categorized as treated, untreated and control. Of the common fragments sequenced by both methods, more mutations and haplotypes were detected by NGS than by Sanger. The NGS method detected three Pfk13, seven Pfcrt, and six Pfmdr1 mutations in our clinical isolates which include rare Pfmdr1 mutations, N504K, N649D, F938Y and S967N, which, to our knowledge, were previously unreported. Nineteen of the 26 (73.1%) isolates had one or more Pfk13 mutations, 9 of the 26 (34.6%) isolates had one or more Pfcrt mutations, and 22 of the 26 (84.6%) isolates had one or more Pfmdr1 mutations. There was moderate prevalence of the K76T mutation (34.6%) and CVIET haplotype (30.8%) associated with chloroquine and amodiaquine resistance and high prevalence of the Pfmdr1 N86 wild type allele (92.3%) and NF (84.6%) haplotype associated with lumefantrine resistance. None of the mutations in the Pfk13 gene associated or confirmed with resistance to artemisinin in South-East Asia was seen. There was a correlation pattern showing that IL-10, IFN-γ and TGF-β levels were markedly lower while the level of cortisol increased but that of dexamethasone-induced protein decreased in treated compared with untreated patients. This result suggests that the interplay between cytokine and endocrine response could have a modulating effect on malaria unresponsive to treatment. This study describes polymorphism in three antimalarial resistance associated genes and how sensitive detection methods such as the NGS can strengthen surveillance for resistant alleles and enhance malaria control efforts.
- ItemOpen AccessDeveloping novel mucoadhesive chitosan based formulations for drug delivery to the urinary bladder(2019-02) Kolawole, O.M.My PhD project aims to develop novel chitosan derivatives (with superior mucoadhesiveness) for transmucosal application. The intravesical route was chosen as the exemplar transmucosal mode of drug delivery due to the limited therapeutic efficiency of conventional bladder cancer formulations. Drug carriers with improved mucoadhesive properties may prolong drug residence in the bladder. First, three chitosan grades were used to prepare chitosan/β-glycerophosphate in situ gelling mixtures and from these grades, the high molecular weight graded chitosan (HCHI) was chosen for chemical derivatisation based on its superior gelation, mucoadhesive and drug release potential. HCHI was conjugated with varying amounts of methacrylate or phenylboronate groups in order to evaluate the influence of the type and amount of conjugated hydrophobic pendant group on their physicochemical and mucoadhesive properties. The boronated and methacrylated chitosans were characterised using 1H NMR and FT- IR. There was good correlation in the extent of hydrophobic modification for methacrylated and boronated chitosans using 1H NMR and ninhydrin test. Methacrylated and boronated chitosan exhibited comparable resistance to pH influence on their solubility. The degree of methacrylate or boronate conjugation had a significant influence on themucoadhesiveness of the drug carriers studied using a urine flow-through technique/fluorescent microscopy as well as a texture analyser, on porcine bladder in vitro. Boronate groups conferred Boronate groups conferred superior mucoadhesive behaviour on chitosan relative to methacrylate groups. Methacrylated chitosan displayed a similar safety profile to the parent chitosan based on MTT assay on UMUC3 bladder cancer cells. The biocompatibility studies of boronated chitosan will be carried out in future studies using bladder cell lines despite the fact that several in vitro and in vivo studies have established the safety of phenylboronic molecules. Methacrylation and boronation of chitosan has been identified as efficient strategies to generatemoremucoadhesive drug carriers which could prolong drug residence time in the bladder thereby improving therapeutic outcomes of bladder cancer patients. These novel polymers were easily synthesised requiringminimal equipment suitable for industrial scale- up. These excipients could be used to formulate affordable transmucosal dosage forms with superior mucoadhesiveness for a variety of biomedical applications.
- ItemOpen AccessSelf assembly of star shaped amphiphiles – Opportunities for drug delivery(Department of Pharmaceutics The School of Pharmacy University of London, 2010-09) Aluko, O.M.In order to study the influence of branching on the self-assembly of PEG amphiphiles, polyethylene glycol (PEG)-based star-shaped have been synthesised and studied as self-assembling systems. Palmitoyl (C16) groups were grafted to 8-armed PEG with differing degrees of palmitoylation (P8PEG1 & P8PEG4). A novel amphiphilic linear analogue (HDPEG) was also synthesised with hexadecyl (C16) pendant groups for comparison. These amphiphiles were characterised using 1H Nuclear Magnetic Resonance, Fourier Transform- Infrared and MALDI-TOF mass spectroscopy. The Pyrene probe was employed to evaluate self assembly properties while Photon Correlation Spectroscopy was used to measure particle size distribution. Molecular architecture and hydrophobic substitution had a profound effect on their self-assembly behavior; as P8PEG4 with branched architecture and the greatest degree of hydrophobic substitution had the lowest polydispersity index. Also, the critical micellar concentration (CMC) for P8PEG4, P8PEG1 and HDPEG were 3, 8 and 15 μM respectively, inferring greater micelle stability with branched architecture and increased hydrophobic substitution. Particle size and morphology were confirmed by Transmission electron microscopy as P8PEG4 and HDPEG formed mixtures of micelles and nanoparticles while a novel core-shell nano- and micro self assembly was observed for P8PEG1. Preliminary drug encapsulation studies on the amphiphiles loaded low amounts of Griseofulvin (0.04-0.09mg/ml with 5mg/ml of polymers). These resulting stable aggregates of PEG-based amphiphiles may be of benefit for drug delivery applications. However, future studies should focus on influence of polymer architecture on drug encapsulation in order to improve their encapsulation efficiency.