Scand J Rheumatology 8: 106-108, I979
PLASMA SALICYLATE LEVELS IN RHEUMATOID ARTHRITIS: A COMPARISON BETWEEN MICRO-ENCAPSULATED AND CONVENTIONAL ASPIRIN Arne Hanson, Ylva Lindroth, Karl-Goran Sjoblom and Frank A. Wollheim
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 12/11/14 For personal use only.
From the Section of Toxicology, Department of Clinical Chemistry and the Division of Rheumatology. Department of Medicine. Malmo General Hospital, University of Lund, Malmo. Sn*eden
ABSTRACT. Ten patients with rheumatoid arthritis were given identical amounts of conventional aspirin (MagnecyP) tablets and micro-encapsulated aspirin (Reumyl") capsules. Steady-state salicylate levels were determined after 4 days' treatment at 8 a m . , 12 noon, 4 pm., 10 p.m. and again at 8 a m . No difference was noted between the levels at 12 noon or 4 p.m. The 10 p.m. levels were slightly though not significantly higher and the 1 s t set of 8 a.m. levels were significantly higher during the capsule administration. A criterion for inclusion was good tolerance of Magnecyl. The clinical effectiveness was not evaluated, hut the observed goad absorption features of Reumyl indicate that this preparation may prove to be of value in long-term treatment.
MATERIAL AND METHODS 11 hospitalized patients with classical rheumatoid arthritis treated with 3.0-4.5 g Magnecyl (acetylsalicylic acid 0.5 g,
magnesium oxide 0.07 g) per day for prolonged periods entered the study. None of the patients had shown any intolerance to the drug. No major changes in the administration of other drugs such as chloroquine, penicillamine or steroids were made during the study. The ASA preparations were administered t.i.d. at 8 a.m., 4 p.m. and 10 p.m. in 7 cases. Three patients in addition took one dose at 12 noon. One patient was taking the ASA at 8 a.m., at 12 noon and at 5 p.m. Blood was drawn. Blood samples were collected after at least 3 days of constant medication at 8 a m . , at 12 noon, at 4 p.m., at 10 p.m. and again at 8 a.m. the next day. In each instance Magnecyl was ad-
In spite of the recent advent of a large number of new non-steroidal anti-inflammatory drugs for the Plasma salicyl8tr treatment of rheumatoid arthritis (RA), acetylmmo\/i 15 salicylic acid (ASA) is still considered a first-line drug by many rheumatologists. However, gastroinT T T T testinal side effects often limit the use of convenI T T I I I tional ASA tablets. In an attempt to reduce gatroin1.o testinal toxicity, enteric coated ASA tablets have been introduced (7, 9, 10, 11). Laine et ai. (8) found higher morning levels of salicylate in patients taking 05 enteric coated tablets, though several authors have reported absorption of enteric coated tablets to be 1 irregular and unpredictable when compared with ,NS, p s, ,N5, ,NS, 0.p1 P dissolved ASA ( 3 , 6 , 9). A new principle of adminisM R MI? M R M R M R 12 now L p.m lOpm earn Earn tering ASA in the form of micro-encapsulated DJY 4 Day 5 granules (Reumyl9 seems to provide satisfactory absorption and to reduce gastrointestinal bleeding Fig. 1 . Plasma salicylate levels in 10 patients with i1. 2). We report here a comparative study in RA- rheumatoid arthritis in steady state ASA tablets and mipatients on salicylate plasma concentrations cro-encapsulated ASA respectively. p-Values refer to t test comparison between the two preparations. M (-)= achieved with such capsules and with conventional Magnecyl" tablets. R (---)=Reumyl@ capsules. N . S . = ASA tablets (MagnecyP). not significant. h mid J Rherrnrorolog~8
Plasma salicylate levels in RA
107
Table I. Plasma ASA levels (in mmolll) after a minimiim of 3 days' intake of Magnec-yP and ReumyP respectively Day 4 Pat.
ASA-dose
8 a.m.
12 noon
16 p.m.
22 p.m.
8 a.m.
F. J.
Magnecyl2 x 3 Reumyl2x 3 Magnecyl2x 3 Reumyl2~3 Magnecyl2 x 3 Reumyl2 x 3 Magnecyl3 x 3 Reumyl3 x 3 Magnecyl2 x4 Reumyl2 x4 Magnecyl2 x 3 Reumyl2 x 3 Magnecyl2 x 3 Reumyl2 x 3 Magnecyl2 x 4 Reumyl2x4 Magnecyl2~4 Reumyl2 x 4 Magnecyl2 x 3 Reumyl2 X 4 Magnecyl Reumyl
0.7 0.8 0.6 1.1 0.3 0.6
I .O I .O 0.8 0.9 0.5 0.6 0.9 1.5 1.1 1.0 0.3 0.5 0.9 0.7 0.5 0.5 1.2 0.6 0.7 0.1 0.79 (0.29) 0.76 (0.39)
1.0 1.2
0.9 1.2 0.9 1.0 0.5 0.8
0.6 0.8 0.5 1.0 0.4 0.6
0.8 1.5
0.8 1.6
M. E.
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 12/11/14 For personal use only.
R. 0. E. J. A. G. G. J. 0. E.
B. P. B. S. G. N. Mean (S.D.)
0.6 1.7 0.9 1.2 0.1 0.3 0.7 0.8 0.4 0.4 1.1
0.8 0.3 0.1 0.57 (0.30) 0.78 (0.47)
ministered before Reumyl. Both preparations were given at identical times and in an identical dose to each individual patient. Regular meals were served at 8.30 a.m., 12.30 p.m. and 5 p.m. throughout the study. One patient was excluded from further evaluation as she did not take Magnecyl and Reumyl at the same time of day. Plasma determination of salicylate concentration was performed by means of a spectrophotofluorometric technique (4).
RESULTS Resulsts of individual salicylate determinations are shown in Table I and Fig. 1 . The diurnal variation in plasma concentration was generally small. One patient (G. N.) behaved differently, showing a substantial variation after both preparations. No difference was noted with regard to ASA levels at 12 noon and 4 p.m. Reumyl resulted in significantly higher ASA levels in the samples taken at 8 a.m. on the last day of each period (p
PLASMA SALICYLATE LEVELS IN RHEUMATOID ARTHRITIS: A COMPARISON BETWEEN MICRO-ENCAPSULATED AND CONVENTIONAL ASPIRIN Arne Hanson, Ylva Lindroth, Karl-Goran Sjoblom and Frank A. Wollheim
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 12/11/14 For personal use only.
From the Section of Toxicology, Department of Clinical Chemistry and the Division of Rheumatology. Department of Medicine. Malmo General Hospital, University of Lund, Malmo. Sn*eden
ABSTRACT. Ten patients with rheumatoid arthritis were given identical amounts of conventional aspirin (MagnecyP) tablets and micro-encapsulated aspirin (Reumyl") capsules. Steady-state salicylate levels were determined after 4 days' treatment at 8 a m . , 12 noon, 4 pm., 10 p.m. and again at 8 a m . No difference was noted between the levels at 12 noon or 4 p.m. The 10 p.m. levels were slightly though not significantly higher and the 1 s t set of 8 a.m. levels were significantly higher during the capsule administration. A criterion for inclusion was good tolerance of Magnecyl. The clinical effectiveness was not evaluated, hut the observed goad absorption features of Reumyl indicate that this preparation may prove to be of value in long-term treatment.
MATERIAL AND METHODS 11 hospitalized patients with classical rheumatoid arthritis treated with 3.0-4.5 g Magnecyl (acetylsalicylic acid 0.5 g,
magnesium oxide 0.07 g) per day for prolonged periods entered the study. None of the patients had shown any intolerance to the drug. No major changes in the administration of other drugs such as chloroquine, penicillamine or steroids were made during the study. The ASA preparations were administered t.i.d. at 8 a.m., 4 p.m. and 10 p.m. in 7 cases. Three patients in addition took one dose at 12 noon. One patient was taking the ASA at 8 a.m., at 12 noon and at 5 p.m. Blood was drawn. Blood samples were collected after at least 3 days of constant medication at 8 a m . , at 12 noon, at 4 p.m., at 10 p.m. and again at 8 a.m. the next day. In each instance Magnecyl was ad-
In spite of the recent advent of a large number of new non-steroidal anti-inflammatory drugs for the Plasma salicyl8tr treatment of rheumatoid arthritis (RA), acetylmmo\/i 15 salicylic acid (ASA) is still considered a first-line drug by many rheumatologists. However, gastroinT T T T testinal side effects often limit the use of convenI T T I I I tional ASA tablets. In an attempt to reduce gatroin1.o testinal toxicity, enteric coated ASA tablets have been introduced (7, 9, 10, 11). Laine et ai. (8) found higher morning levels of salicylate in patients taking 05 enteric coated tablets, though several authors have reported absorption of enteric coated tablets to be 1 irregular and unpredictable when compared with ,NS, p s, ,N5, ,NS, 0.p1 P dissolved ASA ( 3 , 6 , 9). A new principle of adminisM R MI? M R M R M R 12 now L p.m lOpm earn Earn tering ASA in the form of micro-encapsulated DJY 4 Day 5 granules (Reumyl9 seems to provide satisfactory absorption and to reduce gastrointestinal bleeding Fig. 1 . Plasma salicylate levels in 10 patients with i1. 2). We report here a comparative study in RA- rheumatoid arthritis in steady state ASA tablets and mipatients on salicylate plasma concentrations cro-encapsulated ASA respectively. p-Values refer to t test comparison between the two preparations. M (-)= achieved with such capsules and with conventional Magnecyl" tablets. R (---)=Reumyl@ capsules. N . S . = ASA tablets (MagnecyP). not significant. h mid J Rherrnrorolog~8
Plasma salicylate levels in RA
107
Table I. Plasma ASA levels (in mmolll) after a minimiim of 3 days' intake of Magnec-yP and ReumyP respectively Day 4 Pat.
ASA-dose
8 a.m.
12 noon
16 p.m.
22 p.m.
8 a.m.
F. J.
Magnecyl2 x 3 Reumyl2x 3 Magnecyl2x 3 Reumyl2~3 Magnecyl2 x 3 Reumyl2 x 3 Magnecyl3 x 3 Reumyl3 x 3 Magnecyl2 x4 Reumyl2 x4 Magnecyl2 x 3 Reumyl2 x 3 Magnecyl2 x 3 Reumyl2 x 3 Magnecyl2 x 4 Reumyl2x4 Magnecyl2~4 Reumyl2 x 4 Magnecyl2 x 3 Reumyl2 X 4 Magnecyl Reumyl
0.7 0.8 0.6 1.1 0.3 0.6
I .O I .O 0.8 0.9 0.5 0.6 0.9 1.5 1.1 1.0 0.3 0.5 0.9 0.7 0.5 0.5 1.2 0.6 0.7 0.1 0.79 (0.29) 0.76 (0.39)
1.0 1.2
0.9 1.2 0.9 1.0 0.5 0.8
0.6 0.8 0.5 1.0 0.4 0.6
0.8 1.5
0.8 1.6
M. E.
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 12/11/14 For personal use only.
R. 0. E. J. A. G. G. J. 0. E.
B. P. B. S. G. N. Mean (S.D.)
0.6 1.7 0.9 1.2 0.1 0.3 0.7 0.8 0.4 0.4 1.1
0.8 0.3 0.1 0.57 (0.30) 0.78 (0.47)
ministered before Reumyl. Both preparations were given at identical times and in an identical dose to each individual patient. Regular meals were served at 8.30 a.m., 12.30 p.m. and 5 p.m. throughout the study. One patient was excluded from further evaluation as she did not take Magnecyl and Reumyl at the same time of day. Plasma determination of salicylate concentration was performed by means of a spectrophotofluorometric technique (4).
RESULTS Resulsts of individual salicylate determinations are shown in Table I and Fig. 1 . The diurnal variation in plasma concentration was generally small. One patient (G. N.) behaved differently, showing a substantial variation after both preparations. No difference was noted with regard to ASA levels at 12 noon and 4 p.m. Reumyl resulted in significantly higher ASA levels in the samples taken at 8 a.m. on the last day of each period (p
