Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.

Assessment of Lipid Peroxidation Levels and Total Antioxidant Status in Chronic and Aggressive Periodontitis Patients: An in vivo Study.

INTRODUCTION: Periodontitis is a common problem affecting a significant population of the world. For the assessment of oxidative stress of an individual, total oxidation status (TOS) and total antioxidant capacity (TAOC) are the significant biomarkers. Hence, we planned the present study to assess malondialde-hyde (MDA), TOS, TAOC levels, and oxidative stress index (OSI) in generalized aggressive periodontitis (GP) and chronic periodontitis (CP) patients. MATERIALS AND METHODS: The present study included assessment of 40 CP patients, 40 GP patients, and 40 healthy controls. Clinical assessment of all the subjects was done by measuring the probing depth (PD), clinical attachment (CL), gingival index (GI), gingival bleeding index (GBI), and plaque index (PI). Salivary and serum samples were taken and assessed by standard procedures as described previously in the literature. All the values were assessed and compared. RESULTS: Significant results were obtained while comparing all the periodontal parameters in between various study groups. Mean serum MDA levels in the CP, GP, and control group were found to be 0.68, 0.65, and 0.61 µM respectively. Statistically nonsignificant results were obtained while comparing the serum MDA levels in between the three study groups. Significant results were obtained while comparing the mean serum and salivary TOS values, TAOC values, and OSI in between various study groups. CONCLUSION: In periodontitis patients, oxidative stress was significantly higher in comparison with healthy subjects. CLINICAL SIGNIFICANCE: Oxidative parameters do play a significant role in the pathologic profile of periodontitis.