- Email: [email protected]
Frölich replies to botting and vane
LETTERS Friilich replies to Botting and Vane
series Advances in Prostaglandin, Thromboxane and Leukotriene Research. However, Ref. 52 can be Selectivit ancl meaningful classification of NSAlDs based on in found in volume 22 of this series, and vitro an dyin vivo analysis Szczeklik states on page 186 that Botting and Vane criticize my inter‘Patients with aspirin sensitivca The letter by Botting and Vane quesasthma can safely take sodium tions my statement that salicylate is a pretation that the number 2.8 supports this view; it appears as though salicylate ...’ (please see page 33, line selective cyclooxygenase 2 (COX-2) inhibitor’. This issue concerns both in these authors think that a ratio of less 10, ~33, right hand column of m! than 1 (IC,,COX-2/IC,,COX-1) is a Rezlicrcl). z&o and in vivo data. The in vitro necessary criterion for describing a data of Mitchell et ~1.2achieved from In response to Botting and Vane’s drug as COX-2 selective. J 744.2 lipopolysaccharide-activated other comments, the reference on line The numbers of COX-2/COX-1 macrophages, which express a COX-2 7 of page 33, right-hand column, ratios differ widely between irz z>itrO should be 52 not 51, and on line 15 enzyme, and bovine aortic endothetest systems and a single number by lial cells, which express a COX-1 the reference should be 53. itself is not interpretable (for an inenzyme, produced a COX-2 / COX-1 J. C. Frtilich depth discussion, see Ref. 5). IC,, ratio of 2.8; this number was HannoverMedical School, cited in Table 1 of my Reviezcl. Using However, the ratios become interinstituteof ClinicalPharmacology, D-30625Hannover, pretable in a comparative context the same model, aspirin shows a ratio Germany. between nonsteroidal antiinflammaof 166 and meloxicam of 0.8. In vivo data in humans show that salicylate tory drugs, as shown in Table 1 (Ref. References l), and when viewed in the context of does not inhibit platelet aggregation 1 FrGlich, J. C. (1997) Trcvds Phnmmvl. Sci. 18, 3&34 (COX-1) at maximally tolerable antihuman in vivo data (no inhibition of 2 Mitchell, J. A. rt nl. (1994) I’m.. Nat/. inflammatory doses”, nor does it platelet aggregation by salicylate, no Amd. Sci. U. 5. A. 90, 1169S11697 increase gastrointestinal blood loss4, gastrointestinal blood loss). From 3 Rosenkranz, B, Fischer, C. and Frolich, which is thought to be caused by J. C. (1986) Br. I. C/iv. Phnrrtmvl. 21, this point of view salicylate is a selec309-317 COX-1 inhibition. From these data I tive inhibitor of COX-2. 4 Physicims Desk R+rmce. Medrrnl drew the conclusion that salicylate is It is further stated that Ref. 52 does Ecotmr~ics D&n (1993) Montvale, 1351 a fairly selective COX-2 inhibitor. not appear in any volume of the 5 Pairet, M. ci (21.(in press)
International Union of Pharmacology Forthcoming meetings 1997 Advances in Serotonin Receptor Research In collaboration
with the Serotonin
Club
San Francisco, USA B-10 October 1997 1998 1st IUPHAR Conference on Receptor Mechanisms: Principles of Agonism Merano, Italy 23-25 July 1998 Programme
details and registration information can be obtained from:
for these meetings
IUPHAR Media 68 Half Moon Lane, London, UK SE24 9JE And via the IUPHAR WWW site at http: / /www.medfac.unimelb.edu.au /iuphar / TIPS
-September
1997
(Vol.
18)
313
series Advances in Prostaglandin, Thromboxane and Leukotriene Research. However, Ref. 52 can be Selectivit ancl meaningful classification of NSAlDs based on in found in volume 22 of this series, and vitro an dyin vivo analysis Szczeklik states on page 186 that Botting and Vane criticize my inter‘Patients with aspirin sensitivca The letter by Botting and Vane quesasthma can safely take sodium tions my statement that salicylate is a pretation that the number 2.8 supports this view; it appears as though salicylate ...’ (please see page 33, line selective cyclooxygenase 2 (COX-2) inhibitor’. This issue concerns both in these authors think that a ratio of less 10, ~33, right hand column of m! than 1 (IC,,COX-2/IC,,COX-1) is a Rezlicrcl). z&o and in vivo data. The in vitro necessary criterion for describing a data of Mitchell et ~1.2achieved from In response to Botting and Vane’s drug as COX-2 selective. J 744.2 lipopolysaccharide-activated other comments, the reference on line The numbers of COX-2/COX-1 macrophages, which express a COX-2 7 of page 33, right-hand column, ratios differ widely between irz z>itrO should be 52 not 51, and on line 15 enzyme, and bovine aortic endothetest systems and a single number by lial cells, which express a COX-1 the reference should be 53. itself is not interpretable (for an inenzyme, produced a COX-2 / COX-1 J. C. Frtilich depth discussion, see Ref. 5). IC,, ratio of 2.8; this number was HannoverMedical School, cited in Table 1 of my Reviezcl. Using However, the ratios become interinstituteof ClinicalPharmacology, D-30625Hannover, pretable in a comparative context the same model, aspirin shows a ratio Germany. between nonsteroidal antiinflammaof 166 and meloxicam of 0.8. In vivo data in humans show that salicylate tory drugs, as shown in Table 1 (Ref. References l), and when viewed in the context of does not inhibit platelet aggregation 1 FrGlich, J. C. (1997) Trcvds Phnmmvl. Sci. 18, 3&34 (COX-1) at maximally tolerable antihuman in vivo data (no inhibition of 2 Mitchell, J. A. rt nl. (1994) I’m.. Nat/. inflammatory doses”, nor does it platelet aggregation by salicylate, no Amd. Sci. U. 5. A. 90, 1169S11697 increase gastrointestinal blood loss4, gastrointestinal blood loss). From 3 Rosenkranz, B, Fischer, C. and Frolich, which is thought to be caused by J. C. (1986) Br. I. C/iv. Phnrrtmvl. 21, this point of view salicylate is a selec309-317 COX-1 inhibition. From these data I tive inhibitor of COX-2. 4 Physicims Desk R+rmce. Medrrnl drew the conclusion that salicylate is It is further stated that Ref. 52 does Ecotmr~ics D&n (1993) Montvale, 1351 a fairly selective COX-2 inhibitor. not appear in any volume of the 5 Pairet, M. ci (21.(in press)
International Union of Pharmacology Forthcoming meetings 1997 Advances in Serotonin Receptor Research In collaboration
with the Serotonin
Club
San Francisco, USA B-10 October 1997 1998 1st IUPHAR Conference on Receptor Mechanisms: Principles of Agonism Merano, Italy 23-25 July 1998 Programme
details and registration information can be obtained from:
for these meetings
IUPHAR Media 68 Half Moon Lane, London, UK SE24 9JE And via the IUPHAR WWW site at http: / /www.medfac.unimelb.edu.au /iuphar / TIPS
-September
1997
(Vol.
18)
313