Ceftriaxone pharmacokinetics following multiple intramuscular dosing.

The steady-state pharmacokinetics and tolerance of ceftriaxone after multiple i.m. doses of 0.5 and 1 g q12 h for 3.5 days were investigated in 12 healthy, adult volunteers. Ceftriaxone was rapidly absorbed after i.m. administration with mean peak times ranging from 1.3 to 1.9 h. Steady-state plasma concentrations were apparent after the third dose of both dosage regimens, with trough plasma concentrations of 24 +/- 6 and 39 +/- 8 micrograms/ml (mean +/- SD) after the 0.5 and 1 g q12 h regimens, respectively. Multiple i.m. administrations of ceftriaxone did not alter its elimination half-life; however, small increases were observed in the plasma clearance and volume of distribution at the 1-g regimen. These increases were attributed to the non-linear binding of ceftriaxone to human plasma proteins, and are therapeutically unimportant. Ceftriaxone was well tolerated and serious or lasting adverse reactions were not encountered in the study.

The influence of liver dysfunction on the pharmacokinetics of carprofen.

The pharmacokinetics of the investigational agent carprofen were examined in 12 patients with liver dysfunction (hepatic cirrhosis) and in six normal volunteers following single 100-mg oral administration of carprofen. In addition, three patients with acute hepatitis received a single 100-mg dose during the acute phase of the disease, and two of these patients received the same dose after they had convalesced. The pharmacokinetic parameters and urinary excretion data did not differ significantly (P greater than 0.05) between patients with hepatic cirrhosis and healthy volunteers. The mean +/- SD area under plasma concentration-time curve and apparent oral plasma clearance values were 57.8 +/- 11.7 micrograms X h/mL and 30.0 +/- 6.3 mL/min, respectively, in patients and 52.4 +/- 11.3 micrograms X h/mL and 33.1 +/- 7.2 mL/min in normals. The respective harmonic mean elimination half-lives were 10.5 and 9.4 hours. The 0-24 hour urinary recovery of intact drug and the glucuronide conjugate were 7.0 +/- 4.9% and 28.9 +/- 11.0%, respectively, in patients compared to 5.5 +/- 7.1% and 20.1 +/- 12.3% in normal subjects. The results of this study showed that liver dysfunction (hepatic cirrhosis) had no effect on the pharmacokinetic profile of carprofen. In the two patients with acute hepatitis who completed the study, the results suggest that the apparent oral clearance of carprofen may increase during the acute phase of the disease.

Effects of indomethacin and carprofen on renal homeostasis in rheumatoid arthritis patients and in healthy individuals.

The influence of carprofen and indomethacin on renal salt and water homeostasis was investigated. Carprofen is a new nonsteroidal antiinflammatory drug that is currently undergoing clinical trials in the United States. Both drugs were administered in usual clinical doses to steady state in six healthy individuals and in six individuals with rheumatoid arthritis. Blood pressure, weight, plasma renin activity, urine volume, creatinine clearance, fractional excretion of sodium and potassium, and free water reabsorption were determined. Both drugs were found to suppress plasma renin activity. Indomethacin suppressed plasma renin activity more than carprofen. Neither drug produced clinically significant changes in any of the other parameters. In healthy individuals and in patients with rheumatoid arthritis renal homeostatic mechanisms may compensate for the salt- and water-retaining effects of nonsteroidal antiinflammatory drugs.

Origin of the osseous bioelectric potentials: a review.

Recently, an electrophysical approach has been applied to the study of the long bone in order that a more complete understanding of its growth and structural integrity become available. Experimental studies have indicated that weak electric fields may be detected in living bone, in vivo, as the result of externally applied loads, normal weight bearing and pulsatile blood flow. In addition, physiological information may be derived from these electropotentials as functions of their magnitude and polarity. Several sources of these natural osseous bioelectric potentials have been proposed including piezoelectricity, electrokinetic phenomena, p-n semi-conductor junctions, pyroelectricity and photoelectricity. In this paper, these sourcesof bioelectricity are examined, their origins elucidated and their importance ranked in accordance with the maintenance of the structural integrity of the bone.