Bio-Immunoassay for Staphylokinase in Blood

SummaryA bio-immunoassay (BIA) for the determination of staphy-lokinase (STA) activity in a plasma milieu has been developed. MA-7H11, a murine monoclonal antibody raised against STA, which has a high affinity for STA but does not interfere with the complex formation between plasmin(ogen) and STA or with plasminogen activation by STA, was coated on microtiter plates at a concentration of 4 μg/ml. STA-containing samples were incubated overnight at 4° C and, after extensive washing, bound STA was quantitated by incubation with plasminogen (final concentration 0.5 μM) for 1 h at 37°C, followed by determination of generated plasmin from the absorbance at 405 nm 10 min after addition of the chromogenic substrate S-2403 (final concentration 0.3 mM). Calibration curves constructed with natural (STAN) or recombinant (STAR) STA were linear between approximately 1 and 10 nM, with a lower detection limit of ≤ 1 nM in buffer and in plasma of the human, baboon or hamster.Following bolus injection of STAR in hamsters, the disposition rate of STAR activity from plasma, determined with the BIA correlated very well (r = 0.98) with that of STAR-related antigen determined by ELISA, indicating that STAR is cleared in a functionally active form. The initial half-life was about 2 min, as determined with both methods. Following continuous intravenous infusion over 1 h in baboons, the plasma clearance of STAR activity, determined from the infusion rate and the steady-state plasma level of STAR activity, ranged between 45 and 62 ml/min for doses of STAR between 0.063 and 0.250 mg/kg.

Ridogrel Inhibits Systemic and Renal Formation of Thromboxane A2 and Antagonizes Platelet Thromboxane A2/Prostaglandin Endoperoxide Receptors upon Chronic Administration to Man

SummaryThe effects of ridogrel, a dual thromboxane A2 (TXA2) synthase inhibitor and TXA2/prostaglandin (PG) endoperoxide receptor antagonist, on systemic and renal production of prostaglandins and on platelet TXA2/PG endoperoxide receptors was evaluated upon chronic administration (300 mg b. i. d. orally, for 8 and 29 days) to man. Such a medication with ridogrel inhibits the systemic as well as the renal production of TXA2 as measured by the urinary excretion of 2,3-dinor-TXB2 and TXB2 respectively without inducing significant changes in systemic or renal PGI2 production. Simultaneously with the latter effects, the production of TXB2 by spontaneously coagulated whole blood ex vivo is inhibited (>99%) while that of PGE2 and PGF2α is largely increased. Administration of ridogrel causes a three- to five-fold shift to the right of concentration-response curves for U46619 in eliciting platelet aggregation; no tachyphylaxis is observed after 29 days of treatment in this respect. Apart from a reduction of serum uric acid levels with a concomitant increase in urinary uric acid excretion during the first days of treatment, no clinically significant changes in hematological, biochemical, hemodynamic and coagulation parameters occur during the 8 days or 29 days study. The study demonstrates that ridogrel is a potent inhibitor of the systemic as well as renal TXA2 synthase and an antagonist of platelet TXA2/PG endoperoxide receptor in man, covering full activity during 24 h at steady-state plasma level conditions without tachyphylaxis during 29 days of medication. The compound is well tolerated, at least during 1 month of administration.

Plasma Levels of Fluphenazine in Patients Receiving Fluphenazine Decanoate Relationship to Clinical Response

The levels of fluphenazine and fluphenazine sulphoxide in schizophrenic patients who were randomly assigned to receive either 5 mg or 25 mg of fluphenazine decanoate every two weeks were monitored. Patients treated with 25 mg of fluphenazine decanoate required three months to reach a steady-state plasma level, indicating that those patients who are being converted from oral to depot fluphenazine should continue to receive oral supplementation during the first three months of treatment with fluphenazine decanoate. Plasma levels of fluphenazine sulphoxide were lower than levels of fluphenazine. At six and nine months following randomisation, there was a statistically significant relationship between lower fluphenazine plasma levels and an increased risk of psychotic exacerbations. A relatively weak relationship was found between fluphenazine plasma levels and akinesia, but non-significant relationships between fluphenazine levels and other neurological side-effects including akathisia, retardation, and tardive dyskinesia. Monitoring the plasma levels may be helpful to clinicians who are attempting to treat stabilised patients with the lowest effective dose of fluphenazine decanoate.