The urinary excretion of pyridinoline and deoxypyridinoline during rheumatoid arthritis therapy with infliximab.

Rheumatoid arthritis is a systemic disease that causes inflammation and joint destruction. As a result of pathological destruction in bone and cartilage, crosslinks in collagen are resorbed more rapidly. This causes a rise in circulating collagen crosslink levels and their urinary excretion. In RA, apart from the crosslink resorption at the site of inflamed joints, there may be increased resorption due to general bone loss associated with disease activity. The aim of this study was to evaluate the influence of therapy with infliximab on urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPYR) as a markers of collagen degradation and its correlation with clinical and biochemical parameters of disease activity. Seventeen patients with active rheumatoid arthritis treated with infliximab were recruited into the study. The therapy resulted in the reduction in the symptoms of RA and urinary excretion of PYD and DPYR. The urinary excretion of PYD correlated with a number of swollen joints, morning stiffness, CRP and ESR. The urinary excretion of DPYR correlated during infliximab therapy with the number of swollen and tender joints and morning stiffness. The measurement of urinary excretion of PYR and DPYR may give insight into bone metabolism and help us to better understand the actual changes in bone and cartilage caused by RA and its treatment.

[Effect of hyperlipidemia on pharmacodynamics of propranolol and atenolol]. / Wplyw hiperlipidemii pierwotnej na wlasciwosci farmakodynamiczne propranololu i atenololu.

The study was aimed to examine the effects of different presentations of hyperlipidemia on the pharmacodynamics of lipophilic propranolol and hydrophilic atenolol. Thirty subjects were divided into four study groups: the normolipemic subjects, patients with hypercholesterolemia, hypertriglyceridemia and patients with mixed form of hyperlipidemia. The drugs were administered orally at a single dose of 80 mg propranolol and 100 mg atenolol, using a cross-over study design. The plasma concentrations of propranolol and atenolol were determined using high-performance liquid chromatography (HPLC). Heart rate as well as systolic and diastolic blood pressure were evaluated in relation to the serum drug concentrations. In the light of the results obtained, the following conclusions were drawn: 1) hyperlipidemia affects pharmacodynamic properties of lipophilic propranolol and hydrophilic atenolol, 2) a modification of the drug dosage in hyperlipidemia is warranted.

Comparative pharmacokinetics of propranolol and atenolol in primary hyperlipidemia.

The study was aimed to examine the effects of different types of hyperlipidemia on the pharmacokinetics of lipophilic propranolol and hydrophilic atenolol. Thirty subjects were divided into four study groups: normolipemics, hypercholesterolemics, hypertriglyceridemics, and patients with mixed form of hyperlipidemia. The drugs were administered orally at a single dose of 80 mg for propranolol and 100 mg for atenolol, using a cross-over study design. Pharmacokinetic parameters of the drugs were calculated using a noncompartmental open model. The results of the present study demonstrated a possible influence of dyslipidemia on pharmacokinetics of both the lipophilic and hydrophilic drugs. As for the lipophilic drug propranolol, a significant decrease in elimination rate constant was found (from 0.24 +/- 0.08 h(-1) to 0.16 +/- 0.04 h(-1), p < 0.03) in comparison to normolipemic subjects. In the case of the hydrophilic atenolol, the most marked alterations were also seen in subjects with mixed form of hyperlipidemia, especially significantly lower values of area under the concentration-time curve (8950.8 +/- 2060.5 ng/ml x h and 6715.4 +/- 1813.8 ng/ml x h, p < 0.05) as well as higher elimination rate constant (0.08 +/- 0.03 h(-1) and 0.13 +/- 0.05 h(-1), p < 0.05) in comparison with the controls, respectively. Total body clearance per kg of body weight of propranolol as well as atenolol was not influenced by dyslipidemias. The results of the study indicate that lipid metabolism disturbances might to some extent influence the pharmacokinetics of propranolol and atenolol, with the most significant alterations seen in the patients with mixed form of hyperlipidemia.

Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects.

The lipophilic beta-adrenoreceptor antagonist propranolol and hydrophilic atenolol have been studied to define their pharmacokinetic and pharmacodynamic characteristics in obese patients. A total of 43 subjects were allocated into three study groups: (1) healthy, lean, normolipaemic volunteers, (2) obese normolipaemic subjects, and (3) obese patients with lipid disorders. A crossover method with an interval of 2 weeks was applied for oral 80 mg propranolol and oral 100 mg atenolol administration. Heart rate as well as systolic and diastolic blood pressure were recorded during 24 h. At each time-point of measurement blood serum concentration of propranolol and atenolol were evaluated. Pharmacokinetic parameters of the drugs were calculated using a one-compartment open model for extravascular administration. There were no statistically significant differences in blood serum concentrations of propranolol between the studied groups. The concentrations of atenolol were significantly lower in both normolipaemic and hyperlipidaemic obese subjects. A trend towards increase in Vd/F and Cl/F of propranolol in obese patients with hyperlipidaemia were noted. In the case of water-soluble atenolol, the AUC, C(max), Cl/(F x BW) were significantly lower in obese hyperlipidaemic and normolipaemic patients in comparison with lean subjects. The pharmacodynamic effects of propranolol and atenolol in obese and lean subjects were of similar magnitude. The observed differences between obese and non-obese persons were clinically not relevant.