A dose finding study of the LMWH CY222 (MLT2800) in patients (n=8) has been carried out to < i ) establish an effective dose and <ii) determine the relationship between ex vivo anti-factor Xa levels in plasma and the anticoagulant effect (in vivo suppression of FPA levels). Doses of CY222 were compared to a dose <5000 iu bolus+1500 iu/hr) of unfractionated heparin (UFH) that has been shown to suppress FPA levels during prolonged <>5hr) dialysis (Ireland et al , J Lab Clin Med 103, 643, 1984). CY222 given iv in doses (a) 5000 IC (Institute Choay)u bolus+1500 ICu/hr (b) 10000 IC bolus (c) 10000 ICu bolus+ 1500 ICu/hr (d) 15000 ICu bolus+1500 ICu/hr (e) 20000 ICu bolus (f) 20000 ICu bolus+1500 ICu/hr produced a dose related increase in anti-factor Xa levels (measured with CY222 as standard) and suppression of FPA levels. Dose (f) did not alter KCCT, produced FPA levels that were statistically indistinguishable from those of the UFH regime (indicating comparable anticoagulant effect), but had anti-factor Xa Levels (ICu) that were 2-3 times those of UFH. All samples were also assayed against the proposed LMWH Standard. Plasma levels of CY222 were then found to be 2-3 times lower, so that dose (f) had very similar anti-factor Xa levels to those of UFH. Clinically, doses <c), <d), (e) and (f) were all effective, although increasing amounts of fibrin were visible in the dialyser circuit with decreasing dose. T t is concluded that CY222 has comparable anticoagulant effect to UFH when present at similar anti-factor Xa concentration (measured against the LMWH Standard). CY222 may prove to be an effective alternative to UFH for use in haemodialysis.
Low-dose subcutaneous ketamine for postoperative pain management in Rwanda: a dose-finding study