Correlation between the Physicochemical Property of Some Nonsteroidal Anti-inflammatory Drugs and Changes in Adenosine Triphosphate, Glutathione and Hemoglobin in Rat Erythrocytes

Abstract

This study was conducted to explore the relationship between physicochemical property and toxic effectiveness using rat red blood cells (RBCs). The toxic effectiveness of acid nonsteroidal anti-inflammatory drugs (NSAIDs) was systemically examined by the depletion of intracorpuscular adenosine triphosphate (ATP), glutathione (GSH), and hemoglobin (Hb) at various doses, increased every 5 fmol/RBC. When the RBCs were incubated with NSAIDs, the drugs attained maximum levels within RBC, and the levels were then reduced. The ATP depletion seemed to be observed on the excretion of the drugs prior to the depletions of GSH and Hb. The physicochemical properties of NSAIDs were obtained from QMPRPlus, SMILES code, and CS ChemRaw Ultra. Correlation between their physicochemical properties and their doses for the depletions of ATP, GSH and Hb was performed in comparison with those of the membrane bound enzyme (MBE) inhibiting- and methemoglobin (MHb)-generating drugs. The ATP depletion by NSAIDs was correlated with the GSH depletion and intracorpuscular levels of the drugs, but not with the Hb depletion. The GSH depletion was correlated with the Hb depletion and participated in the lipophilicity of the drugs.

Current status of the therapeutic uses and actions of the preferential cyclo-oxygenase-2 NSAID, nimesulide

“…central or peripheral) antipyretic and other pharmacological properties. Physico-chemical factors are well-known to infl uence pharmacokinetics of NSAIDs (Graf et al, 1975;Brune et al, 1977;Netter et al, 1993) and especially the rate of GI absorption and uptake into infl amed cells or synovial tissues and cerebrospinal fl uids (Netter et al, 1993;Rainsford, 1999aRainsford, , 2004cShimizu et al, 2003;Pehourcq et al, 2004;). NSAIDs with low pKa values (e.g.…”

Evaluation of Formulation Parameters on Permeation of Ibuprofen from Topical Formulations Using Strat-M® Membrane

“…Therefore, topical/transdermal delivery of NSAIDs is preferred as it bypasses hepatic first pass metabolism and also results in targeted effect at the site of inflammation/pain [24]. Majority of the NSAIDs (salicylates, acetic acid derivatives, enol acid derivatives, and propionic acid derivatives) approved by USFDA have similar physicochemical properties (molecular mass, logP, and pK a ) [27][28][29][30]. Hence, it can be assumed that there may be similarities in transdermal permeation for these compounds [29].…”