Pharmacokinetics and clinical evaluations of gentamicin-induced nephrotoxicity in puppies

Background: The study was aimed at investigating the effect of dosing intervals on gentamicin nephrotoxicity in puppies.Methods: Local puppies were assigned to Groups A and B (n=6) and administered gentamicin intramuscularly once (6 mg/kg) or twice (3 mg/kg) daily, respectively, for 5 consecutive days. Biochemical parameters such as urine protein, creatinine, ɤ-glutamyl transferase, as well as serum creatinine (SCR) and urea nitrogen were determined spectrophotometrically using specific kits before and after treatment. Peak and trough serum concentrations of gentamicin were determined by immunoassay on 1st and 5th day treatment. Thereafter, elimination rate constants and corresponding half-lives were calculated.Results: No significant increase in SCR concentrations in both groups was observed, but values on day 7 were slightly above normal. Conversely, there was a significant increase above normal in serum urea nitrogen on days 4 and 7 in Group A, whereas this was observed only on day 7 in Group B. Even though all other biochemical parameters assayed for were within normal, an increasing trend was noticed as the length of treatment days increased in both groups. In both groups, peak serum concentrations of gentamicin did not differ significantly. There was a 4- and 16-fold significant increase in trough levels after the last treatment in Groups A and B, respectively. Although peak and trough concentrations increased with increasing length of treatment, all the values were well below 10 µg/ml and 2 µg/ml, respectively, as required.Conclusion: These suggest the risk of nephrotoxicity following treatment with gentamicin beyond 5 consecutive days irrespective of the dosing interval in puppies

Repurposing of chloroquine and hydroxychloroquine for the management of COVID-19

The Coronavirus Disease-19 (COVID-19) pandemic has impacted adversely on the global health and socio-economic activities. There is currently no evidence-based anti-SARS-CoV-2 drug for COVID-19 therapy. This review highlights some pharmacological properties of chloroquine and hydroxychloroquine and prospects of repurposing them for the treatment of COVID-19. Google scholar was employed in searching relevant published journal articles (n=118) in English. The search was later narrowed down to SARS-CoV-2, pathophysiology of COVID-19, available drugs for the management of COVID-19, clinical trials on repurposing drugs for COVID-19 therapy, and the role of chloroquine and hydroxychloroquine in the treatment of COVID-19. Documented evidence revealed that chloroquine and hydroxychloroquine have antiviral and immune-modulatory properties. Their antiviral effect is due to inhibition of the spike proteins of SARS-CoV-2 from binding to the cellular transmembrane receptors, angiotensin converting enzyme-2 thereby preventing viral infections. Also, sequestration of these drugs into the lysosomes elevates lysosomal pH thus inhibiting lysosomal enzymatic functions vital for viral replication in those cells. Whereas, their immune-modulatory activity averts the inflammatory complications of COVID-19, particularly acute respiratory syndrome, by preventing cytokine storm through suppression of the production and putative release of pro-inflammatory cytokines. The adverse effects from these drugs, notably irreversible retinopathy and cardiac arrhythmia are rare but become life-threatening when they occur. These are minimal with hydroxychloroquine compared to chloroquine. Chloroquine and hydroxychloroquine could be repurposed for managing COVID-19 cases because they are already extensively used for treating acute nonresistant malaria and auto-immune diseases. Also, a viable vaccine cannot be available in the near future while there is a pressing need for treatments to lower the daily rise in morbidity and mortality associated with the disease. Nevertheless, we suggest that emphasis should be on hydroxychloroquine because of its superior antiviral effect and clinical safety

Toksični učinci nekih biljaka roda Euphorbia na hematološke i biokemijske pokazatelje u štakora

The toxic effects of 5 suspected poisonous plants of the genus Euphorbia (Euphorbia balsamifera Aiton, E. heterophylla L., E. hirta L., E. hyssopifolia L., and E. lateriflora Schum and Thonn), which are commonly found in the Nigerian pasture, were evaluated in albino rats using crude aqueous extracts for 14 days. Changes in haematological as well as biochemical parameters were used as indices of toxicosis. Clinical signs were also noted. The extracts of all the plants caused dullness, anorexia, stairy haircoat, and 20% mortality rate in E. hirta and E. hyssopifolia. Animals that received the extracts of E. balsamifera, E. hyssopifolia, E. heterophylla, and E. lateriflora appeared to show an excitatory effect. However, it was noted that the animals became dull afterwards. E. hirta produced the highest mortality rate. The crude extracts that were administered orally produced anaemia in the animals. While E. heterophylla, E. hyssopifolia and E. lateriflora caused leucopaenia, E. hirta and E. balsamifera caused leucocytosis. Three of the plants caused a significantly increased (P<0.05) level of total protein; the remaining 2 (E. balsamifera and E. heterophylla) caused an insignificant increase. While all the plants caused a significant increase in the level of albumin, the reverse was the case for globulin. All the plants also caused significant increase in levels of ALT and AST.Istraženi su toksični učinci pet na otrovnost sumnjivih biljaka roda Euphorbia (Euphorbia balsamifera Aiton, E. heterophyla L., E. hirta L., E. hyssopifolia L. i E. lateriflora Schum et Thonn), koje se često nalaze na pašnjacima Nigerije. Istraživanje je provedeno na albino štakorima upotrebom sirovog vodenog iscrpka u tijeku 14 dana. Hematološki i biokemijski poremećaji uzeti su kao pokazatelji toksičnosti. Promatrani su i klinički znakovi trovanja. Iscrpci svih biljaka uzrokovali su potištenost, anoreksiju i neuredan dlačni pokrivač, a iscrpci E. hirta i E. hyssopifolia 20%-tni pomor štakora. životinje koje su dobivale iscrpak E. balsamifera, E. hyssopifolia, E. heterophyla i E. Lateriflora pokazivale su najprije razdražljivost, a potom potištenost. E. hirta uzrokovala je najveći stupanj pomora. Sirovi iscrpci davani peroralno uzrokovali su anemiju. Dok su E. heterophyla, E. hyssopifolia i E. ateriflora uzrokovale leukopeniju, E. hirta i E. balsamifera uzrokovale su leukocitozu. Tri pretraživane biljke uzrokovale su značajno (P<0,05), a preostale dvije (E. balsamifera i E. heterophyla) neznatno povećanje razine ukupnih proteina. Za razliku od razine globulina, sve su biljke uzrokovale značajno povećanje razine albumina. Sve su također dovele do značajnog povećanja razine ALT i AST