Introduction: Chronic renal failure (CRF) is a progressive loss of renal function that lead to reduced sodium filtration and inappropriate suppression of tubular reabsorption that ultimately leads to volume expansion. To improve treatment outcomes, the aim of this study was to evaluate the possible renoprotective effect of tadalafil and furosemide, individually and in combination, in both conventional and nanoforms in adenine-induced CRF rat-model. Methods: Addition of 0.75% adenine to the diet of rats for 4 weeks gained general acceptance as a model to study kidney damage as this intervention mimicked most of the structural and functional changes seen in human chronic kidney disease Urine analysis, histopathological changes and immunohistochemical expression of caspase-3 and interleukin-1β (IL-1β) in renal tissues were performed. Results: Our results showed that the combination of tadalafil and furosemide using conventional and nanoparticle formulations revealed a beneficial therapeutic effect in the treatment of CRF. This was demonstrated by improvement of urinary, serum and renal tissue markers as indicative of organ damage. This was also reflected on the reduction of tubular expression of KIM-1 and NGAL. Immunohistochemical studies showed that significant increase in the number of apoptotic tubular cells indicated by increased expression of caspase-3 in CRF. These deteriorated renal cellular changes were improved by the treatment of rats with the investigated drugs. Results from ELISA showed that IL-1β was reduced by such treatment in kidney tissue. Conclusion: Tadalafil and furosemide improved the biochemical, histopathological and immunohistochemistry changes in adenine-induced CRF which strongly support the renopreventive effects of investigated drugs in particular the nanoparticle forms.

Therapeutic drug monitoring (TDM) is a teamwork clinical pharmacokinetic services aimed to optimize pharmacotherapy of certain drugs such as those with a narrow therapeutic range, complicated pharmacokinetics. It involves the determination of drug level in blood samples taken at the appropriate time. Interpretation of results requires integration of pharmacokinetics, the pharmacodynamics of the drug and the patient’s clinical profile. To be cost-effective the service should be optimized. This review was written by experts from different developing countries to highlight the fundamentals of the service and provide suggestions for its optimization. These cover the rationale of requesting drug level, design of request form, optimal sampling, and analytical tools. guidelines for appropriate interpretation of drug levels; completeness of the roles of the qualified medical team; continuing education and skills development; involve the patients in improving the service, conducting relevant research; use PK software and integration of TDM with pharmacogenomics