The pharmacokinetics of artemisinin after oral, intramuscular and rectal administration to volunteers

The pharmacokinetics after oral, intramuscular and rectal administration of artemisinin, a new potent antimalarial drug, to healthy volunteers has been examined. The study was set-up as a four-way cross-over design with a wash-out period of one week between the test days. In ten volunteers artemisinin concentrations in serum were monitored using a reversed phase HPLC assay with UV detection after derivatization. After oral administration, artemisinin was rapidly but incompletely absorbed, the mean absorption time was 0.78 h and the bioavailability relative to the intramuscularly injected suspension in oil 32%. The mean residence time of the latter (10.6 h) was 3 times that of the oral formulation (3.4 h). This seems to enable a twice daily dosage regimen for the intramuscular oil injection, while the oral formulation necessitates a more frequent dosing interval. After intramuscular injection and rectal administration of an aqueous suspension, very low and variable artemisinin concentrations in serum were observed, probably indicating a poor and erratic absorption.     

Static footprint analysis: a time-saving functional evaluation of nerve repair in rats.

Walking track analysis is a widely accepted technique for functional evaluation after sciatic nerve repair in rats, but it is labour-intensive. In 2000, Bervar described a time-saving digitised static footprint analysis. In that study there were good correlations between the traditional sciatic function index (SFI) and the newly-developed static sciatic index (SSI) and static toe spread factor (TSF), respectively. Despite promising results, static footprint analysis is still not widely used. The present study was designed to validate it. After transection of the sciatic nerve, end-to-end repair was assessed using video recorded dynamic and static footprints in 45 Wistar rats. We found an even better correlation between the SFI and both the SSI and the static TSF. In conclusion, static footprint analysis is a time-saving and easy technique for accurate functional assessment of peripheral nerve regeneration in rats.     

Ethylenediamine,profile of a sensitizing excipient

Ethylenediamine is an excipient with many industrial and pharmaceutical uses. It is included in creams as a stabilizer and in aminophylline as the counter ion of theophylline. Ethylenediamine is one of the most frequent contact sensitizers, producing local and generalized reactions. Besides, many cases of systemically induced dermatitis have also been described both after oral, rectal and intravenous use. Inhalation of ethylenediamine or aminophylline dust may provoke rhinitis and asthmatic reactions. In contrast to these delayed reactions only one immediate reaction of the urticarial type after intravenous use has been described. Ethylenediamine shows cross-reactions with antihistamines of the ethylenediamine derivative group, with edetate, other amines, piperazine and hydroxyzine. Ethylenediamine shows a short half-life of about 0.55 h and a small volume of distribution of 0.133 l/kg. After oral administration its bioavailability is about 0.34, due to a substantial first-pass effect. Renal excretion of the unchanged substance amounts to only about 18% after intravenous and 3% after oral administration. It behaves independently from theophylline after administration of aminophylline. Good alternatives are now available for the pharmaceutical applications of ethylenediamine. Theophylline itself is well absorbed orally; for the intravenous administration theN-methylglucamine salt is sufficiently soluble. Suppositories containing pure theophylline are commercially available in some countries, but the experience with this product is relatively small.     

The use of intraperitoneal xenon for early diagnosis of acute mesenteric ischemia

We evaluated the technique of intraperitoneal use of xenon Xe 133, previously described for the diagnosis of early intestinal strangulation obstruction in rats and dogs, for the recognition of acute mesenteric vascular occlusion in these animals. 133Xe was injected intraperitoneally into five groups of six rats: control, sham operation, superior mesenteric artery (SMA) ligation, superior mesenteric vein ligation, and portal vein ligation. Residual gamma-activity was monitored by external counting and camera imaging. At 30 minutes after injection, the activity was significantly higher in the rats from the three groups with vascular ligation than in the control and sham operation animals (P less than 0.001). gamma-Camera images reflected these findings, with positive images only in the rats that underwent vascular ligation. "Blinded" readings of the 30 sets of scans confirmed the diagnostic accuracy of the images. Results were essentially the same in a second series of experiments in eight control dogs and six dogs with balloon occlusion of the SMA. Concentrations of isotope in ischemic intestine ranged from 10(3) to 10(5) times the levels in adjacent normal bowel. These levels and the positive images appeared early, prior to the development of tissue necrosis. The intraperitoneal use of 133Xe therefore continues to show promise for the recognition of patients with early intestinal ischemia.     

Carrots and sticks: impact of an incentive/disincentive employee flexible credit benefit plan on health status and medical costs.

PURPOSE: Employee wellness programs aim to assist in controlling employer costs by improving the health status and fitness of employees, potentially increasing productivity, decreasing absenteeism, and reducing medical claims. Most such programs offer no disincentive for nonparticipation. We evaluated an incentive/disincentive program initiated by a large teaching hospital in western Michigan. METHODS: The HealthPlus Health Quotient program is an incentive/disincentive approach to health promotion. The employer's contribution to the cafeteria plan benefit package is adjusted based on results of an annual appraisal of serum cholesterol, blood pressure, tobacco use, body fat, physical fitness, motor vehicle safety, nutrition, and alcohol consumption. The adjustment (health quotient [HQ]) can range from -$25 to +$25 per pay period. We examined whether appraised health improved between 1993 and 1996 and whether the HQ predicted medical claims. RESULTS: Mean HQ increased slightly (+$0.47 per pay period in 1993 to +$0.89 per pay period in 1996). Individuals with HQs of less than -$10 per pay period incurred approximately twice the medical claims of the other groups (test for linear trend, p = .003). After adjustment, medical claims of employees in the worst category (HQ < -$10 per pay period) were $1078 (95% confidence interval $429-$1728) greater than those for the neutral (HQ between -$2 and +$2 per pay period) category. A decrease in HQ of at least $6 per pay period from 1993 to 1995 was associated with $956 (95% confidence interval $264-$1647) greater costs in 1996 than was a stable HQ. CONCLUSIONS: The HealthPlus Health Quotient program is starting to yield benefits. Most employees are impacted minimally, but savings are accruing to the employer from reductions in medical claims paid and in days lost to illness and disability.