Department of Pharmacology and Pharmacognosy

ATP Binding Cassette sub-family B member 1 (ABCB1) affects disposition of many drugs and thus affects the pharmacokinetics of drugs and ultimately treatment response. Polymorphisms of ABCB1 especially ABCB1 C3435T polymorphism may affect excretion of lopinavir and eventually the pharmacokinetics of lopinavir. Methods: The study design was a historical cohort study and entailed collection of patient data. PureLink® genomic DNA extraction mini kit was used for the extraction and purification of genomic DNA. TaqMan® drug genotyping assay and protocol was used in the DNA amplification and genotyping. Data analysis was done using STATA software version 10. Results: Study participants with the ABCB1 3435 CT genotype had lower creatinine levels after 6 months on lopinavir-based regimens compared with those with the CC genotype (p = 0.001). However, there was no significant association between the ABCB1 C3435T genotypes and creatinine levels at baseline and at the time of switching therapy from first line antiretroviral therapy to second-line antiretroviral therapy which was lopinavir-based. Conclusion: ABCB1 C3435T polymorphism affects creatinine levels 6 months after therapy on lopinavir-based regimens.

Background: Cancer is one of the major causes of death worldwide. Current cancer therapy is costly, it has poor therapeutic outcomes and many side effects. Therefore, new medications are needed. Plants have been used as sources of anticancer drugs. Vepris species have anticancer properties. The purpose of this study is to assess Vepris nobilis, a plant found in Kenya as a potential source of anticancer drugs.Methods: The dichloromethane/methanol (CH2Cl2/MeOH) 1:1 extract of the stem bark of Vepris nobilis led to the isolation of an alkaloid named, 4,6-dimethoxy-7-((3-methylbuta-1,3-dien-1-yl)oxy)furo[2,3-b]quinolone. SwissADME online tool was used to assess the compound’s pharmacokinetic parameters. Pass online tool identified potential targets while protox server described the toxicity of the compound. Chimera and Avogadro softwares were used for molecular docking studies.Results: In-silico pharmacokinetic studies, showed that the isolated compound complied with Lipinski rule of fi...

COVID-19 is noxious and constitutes a raft of adverse multiplier effects. As such, there is urgent need to understand the disease well and take action to mitigate its punitive pathologic & economic outcomes. Comprehending the conduct of the immune system during and after infection may provide fundamental leads to unraveling effective interventions. Some vaccines and drugs have since been validated and made available for emergency use among priority populations. However, these vaccines were developed at an accelerated pace and mainly on the basis of rudimentary immunological & molecular events. Therefore, there is need for continuous revelation of precise and more elaborate hallmarks in order to improve on, or develop more efficacious and safe interventions. Three scientific databases (PubMed, Cochrane and EMBASE) were searched between 1st December, 2020 and 15th January, 2021 for information about immune responses to SARS COV-2. Studies that utilized experimental designs, exhibited ...

Malaria is a deadly infectious parasitic disease that causes devastating morbidity and mortality globally. Despite being a public health concern, an effective vaccine for prevention of the disease remains elusive. Global efforts are exploring possible ways of developing and improving vaccines to counteract the complex nature in which Plasmodium falciparum evades the immune system. A number of vaccines have been developed in the past targeting the various parasitic life cycle stages. Transmission blocker vaccines, such as PpPf S25, target the parasite stages in the mosquito vector. However, these herd vaccines only protect the immunized population. Vaccines targeting blood-stage forms, such as the AMA-1 and MSP-1 vaccines, are challenged by the complex metabolic pathways of erythrocytes and merozoites. Vaccines targeting the pre-erythrocytic sporozoite stage remain the most promising approach thus far. Here, we systematically review the literature on pre-erythrocytic stage vaccines a...

Background : CD4 cell response in patients on second-line therapy has not been evaluated in Kenya. Patients failing second-line are changed to third-line, however, the drugs used for third-line are expensive and unavailable. Therefore, early identification of potential poor responders to treatment would lead to early intervention and thus improve therapy of patients on second-line. Objectives: To identify socio-demographic and treatment related variables that affect CD4 response of HIV-positive patients on second-line regimens in Kenyatta National Hospital (KNH). Methods: A historical cohort study carried out at KNH between January and April 2016 and entailed collection of patient data from the files. The main outcome variable was CD4 cell count.  The predictor variables of interest were sex, age, education level, and ART regimens. Results: All the study participants were on a lopinavir-based regimen. The study involved 84 study participants, 59.5% female study participants and 40.5...

Antimicrobial resistance (AMR) has and continues to pose both development & public health threats across the world. While the scourge is well disseminated globally, persons living in low- & middle-income countries (LMICs) are most at risk. In Kenya, AMR represents a pivotal driver of morbidity & mortality as infections that are resistant to antibiotics have continued to rise lately. Empirical data on the state of AMR in Kenya and other LMICs is conspicuously low or completely lacking. This has significantly muffled intervention strategies as explicit understanding of AMR faculties remains a bottleneck. We conducted a scoping review to understand the nexus between practice of ethical principles of biomedicine & occurrence of AMR. PRISMA guidelines were strictly referenced at every step of this review. PubMed, EMBASE & Cochrane databases were searched using google for relevant articles. A total of 187 articles were initially generated. Several filters were applied in order to develop ...

Introduction: Use of natural products for management of diseases has increased widely due to the belief that natural products are less toxic than conventional medicines. Natural products have been utilised for management of chronic diseases such as diabetes and cancers. Respiratory infections have also been managed using natural products. Allium sativum is one of the natural products that has been utilised in the management of SARS-CoV infections, diabetes and cancer. Methods: This study was aimed at screening bioactive agents in Allium sativum using computational analysis. The targets of the bioactive agents were predicted using SwissTargetPrediction tools. Molecular docking followed, where the docking energies of the bioactive agents to the targets were generated. The bioactive agents were analysed for pharmacokinetics properties using SwissADME as well as toxicity profiles using the ProTox II webserver. The docking scores, toxicities and pharmacokinetics profiles of the bioactive...

Background: The polyol pathway contributes to the development of diabetic complications but can be inhibited by plant phytochemicals. This study aimed at assessing analogs of specific flavonoids that delay onset of microvascular complications with better pharmacokinetic and toxicology profiles. Methods: An in silico study design was employed. The phytochemicals luteolin and quercetin were selected. Analogs were obtained from ZINC database and prepared using Avogadro software. Docking analysis was done using AutoDock Vina embedded in Chimera. Ligand enzyme interaction was carried out using Biovia Discovery studio. Pharmacokinetic and toxicological profiling was carried out using SWISSADME and protox server. A total of 40 analogues were analyzed. Sulindac was used as the comparator besides original phytochemicals. Results: Docking analysis showed both luteolin and quercetin (-9.7) had a slightly stronger affinity for inhibiting aldose reductase compared with sulindac (-9.6). Eight analogues of luteolin and 14 analogues of quercetin showed stronger affinity with the highest registered at-10.6. Both luteolin and quercetin did not violate the Lipinski rule, had high GI absorption, did not cross the blood brain barrier nor were p-glycoprotein substrates, and inhibited CYP1A2, CYP2D6 and CYP3A4. The LD50 of luteolin (3,919 mg/kg) was high indicating excellent safety profile. Quercetin had a low LD50 (159 mg/kg). All 22 analogues exhibited similar pharmacokinetic profiles to their respective phytochemical. However, they did differ in terms of docking strength and toxicology analysis. Six out of the eight luteolin analogues had LD50=3,919 mg/kg, while the remaining had LD50=159 mg/kg. Five quercetin analogues had LD50 of 159 mg/kg, another five had LD50=3,919 mg/kg and the rest had LD50=4,000 mg/kg, while the other two had a LD50 of 5,000 mg/kg. Conclusions: In conclusion, six ZINC compounds similar to luteolin Open Peer Review Approval Status AWAITING PEER REVIEW Any reports and responses or comments on the article can be found at the end of the article.

Background: Tuberculosis is caused by Mycobacterium tuberculosis and is spread through the air. Multidrug-resistant tuberculosis (MDR TB) has become a global health concern. This study focuses on developing alternative compounds to Levofloxacin, Moxifloxacin, Bedaquiline, Kanamycin, Amikacin, Cycloserine, Ethambutol, Pyrazinamide, Linezolid and Streptomycin that can be used to treat patients with multidrug resistance TB. The virtual screening will aid in discovering other possible compounds for use in the management of MDR TB, thereby providing a superior alternative to currently existing medications and aid in eradicating TB. The objective of this study was to identify potential compounds that can be used in managing MDR TB in chronic tuberculosis patients using computational methods. Methods: The Swiss Similarity tool was used to identify similar compounds to the tuberculosis drugs in a ZINC database. Compounds more similar to the tuberculosis drugs were selected and used to test the molecular docking with their respective targets. The pharmacokinetics and toxicity profiles of the selected compounds were analyzed using Swiss ADME and Pro Tox Server, respectively. Results: Overall, 90 compounds had higher binding energies than the medications, 88 had lower binding energies, and 14 had binding energies that were equivalent to those of the drugs. Only 14 of the 200 compounds lacked CYP inhibition, were p-glycoprotein substrates, had superior docking scores to the compounds, and fell into toxicity classes V and VI. Conclusions: The 14 potential compounds should undergo further in vivo and in vitro studies to develop new compounds for managing multidrug-resistant tuberculosis.