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Comparison of absorption of vitamin A after oral and intramuscular administration in normal children
COMPARISON OF ABSORPTION OF VITAMIN A A F T E R ORAL AND INTRAMUSCULAR ADMINISTRATION IN NORMAL C H I L D R E N GONZALO CIENFUEGOS,
M.D.
SANTIAGO, C H I L E
administration of vitamin A has been widely recommended T HandE parenteral used, especially for patients having pancreatic cystic fibrosis. After the work of Andersen 1, ~ and other authors, the pulmonary changes associated with pancreatic achylia have been related to vitamin A deficiency, because squamous metaplasia of the epithelium has been found, but whether the lack of the vitamin is the only cause of the pathologic lesions is still unl~nown. At any rate, the pulmonary condition often does not improve despite the a~mlnistration of large amounts of the vitamin given over long periods of time. This negative result, obtained by all the people who have worked with fibrocystic disease of the pancreas, was brought to my attention by experience at Bobs Roberts Hospital in Chicago in treating a patient who received 50,000 I. U. intramuscularly daily during fifteen days and subsequently every third day for six months. Periodical chest x-ray films never showed any improvement whatsoever. May and others 4 have demonstrated that vitamin A when administered orally is not absorbed well by these patients. Experience led us to believe that parenterally administered vitamin was also not absorbed. This was confirmed in our patient by an absorption curve made following intramuscular injection of 10,000 I. U. of vitamin A per kilogram of body weight, which showed no rise whatever in the serum levels of vitamin A. No control data regarding absorption curves following parenteral administration of vitamin A in normal children have been found in the literature. A study of the absorption of vitamin A after intramuscular injection in children without abnormalities in digestion or fat metabolism was therefore undertaken. Injectable vitamin A (1 c.c. ~ 50,000 I. U. in sesame oil)* was given in doses of 10,000 I. U. per kilogram of body weight. The same source of vitamin was used for both oral and parenteral tests. The material was injected into the muscles of the buttocks. Blood was obtained at the moment of the administration and three, six, nine, and twenty-four hours after parenteral injection, and after three and six hours when the vitamin was given orally. In some patients receiving the vitamin orally, only fasting and 6-hour specimens of blood were taken, since our chief object was to determine whether these patients had a normal absorption of vitamin A. The determination of the vitamin was made according to the method described by May, and associates. * F r o m the Babies Hospital and D e p a r t m e n t of Pediatrics, Columbia U n i v e r s i t y College of Physicians a n d Surgeons, New York, N. Y. 9The vitamin preparation used in this study w a s made by Endo Products, Inc., Richmond Hill, N'. Y. This w o r k w a s supported b y the Commonwealth Fund. 191
192
THE JOURNAL OF PEDIATRICS TABLE I.
SERUM VITAMIN A AFTER ORAL fiA)MINIBTRATION FASTING 3 HR. LATER 6 HR. LATER 9 VITAMINA -~ l - - ~ ' ~ I N A CAROTENEI I.U./100 CAROTENE] I.U./100 [CAROTENE I.U./100
AGE
DIAGNOSIS NO. (YR.) 1 Rheumatic fever 8 2 Mdni~re's syndrome 9 3 Poliomyelitis 7 convalescent 4 Rheumatic fever 9 5 Rheumatic fever 6 6 Cerebral tumor 9 7 Upper respiratory 2 infection
7/too c.c.]
c.c.
Iv/lO0e.~!
~0.
10.5 9.6 15.3
122 148 155
Iv/leO o.c.]
9.0 9.0 16.0
770 614
4.4 10.2 8.2 25.2
160 154 140 154
3.7 9.8 7.8 28.2
716 549 840 920
7.8 25.4
a~
310 286
T A B L E II. S E R U M V I T A M I N A A F T E R I N T R A M U S C U L A R INJECTION
FASTING CARO- VITATEN~ MIN A 7/100 I.U./100 NO. 1 2 3 4 5 6 7
C.C.
9.0 8.8 15.6 4.6 12.4 7.8 25.0
C.C.
139 142 155 158 101 180 135
3 HR. LATER CAR0TENE
VITAMIN A
~//100 C.C. 9.0 8.6 16.2 4.4 12.2 8.0 25.4
I.U./100 C.C. 139 140 152 150 99 192 198
6HR. LATER O~kRO- VITATENE C.C.
MIN A I.U./lO0 C.O.
10,6 8.8 15.8 4.2 12.6 8.6 25.8
154 142 156 146 91 178 153
~//100
9 HR, LATER CtARO- VITATENE MIN A
-#100 i.u./100 C.O. 10.0 8.6 15.2 4.8 12.2 7.8 25.8
C.O. 156 148 152
24 HR. L A T B CARDTEN]~
VITAM~ 9
~/100 C.O. 10.6 8.8 15.8 4.8
i.u./100 0.0. 140 " 180 184 152
98 178 158
As shown in Table I, all the patients who received vitamin A by the oral route experienced a marked rise in vitamin level after six hours when, according to May and associates, 4 the vitamin A concentration is at its highest level in the plasma. Table II shows that the vitamin was not utilized at all when given parenterally. In some patients the serum vitamin A concentration was assayed twenty-four hours after parenteral administration. This experiment was based on comparable tests performed in dogs by Clausen, s who found that when vitamin A was given intramuscularly, the highest level was obtained after twelve or twenty-four hours. In all our patients from whom we took blood after twenty-four hours, the vitamin concentration was approximately the same as at the beginning. It is concluded that the parenteral administration of vitamin A fails to raise its concentration in the circulating blood. SUMMARY
A comparison has been made between vitamin A absorption curves following oral and parenteral administration of the vitamin in seven children without digestive symptoms. In all cases the oral administration resulted in normal absorption, while the parenteral administration showed little or no evidence of absorption. REFERENCES 1. 2. 8. 4.
Andersen, D. H.: Am. J. Dist. Child 56: 344, 1938. Andersen, D. H.: J. PEDIAT. 15: 763, 1939. Clausen, S. W. : The Harvey Lectures 38: 199, 1943. May, C. D., Blackfan, K. D., McCreary, J. P., and Allen, F. H.: 1167, 1940.
Am. J. Dis. Child 59:
M.D.
SANTIAGO, C H I L E
administration of vitamin A has been widely recommended T HandE parenteral used, especially for patients having pancreatic cystic fibrosis. After the work of Andersen 1, ~ and other authors, the pulmonary changes associated with pancreatic achylia have been related to vitamin A deficiency, because squamous metaplasia of the epithelium has been found, but whether the lack of the vitamin is the only cause of the pathologic lesions is still unl~nown. At any rate, the pulmonary condition often does not improve despite the a~mlnistration of large amounts of the vitamin given over long periods of time. This negative result, obtained by all the people who have worked with fibrocystic disease of the pancreas, was brought to my attention by experience at Bobs Roberts Hospital in Chicago in treating a patient who received 50,000 I. U. intramuscularly daily during fifteen days and subsequently every third day for six months. Periodical chest x-ray films never showed any improvement whatsoever. May and others 4 have demonstrated that vitamin A when administered orally is not absorbed well by these patients. Experience led us to believe that parenterally administered vitamin was also not absorbed. This was confirmed in our patient by an absorption curve made following intramuscular injection of 10,000 I. U. of vitamin A per kilogram of body weight, which showed no rise whatever in the serum levels of vitamin A. No control data regarding absorption curves following parenteral administration of vitamin A in normal children have been found in the literature. A study of the absorption of vitamin A after intramuscular injection in children without abnormalities in digestion or fat metabolism was therefore undertaken. Injectable vitamin A (1 c.c. ~ 50,000 I. U. in sesame oil)* was given in doses of 10,000 I. U. per kilogram of body weight. The same source of vitamin was used for both oral and parenteral tests. The material was injected into the muscles of the buttocks. Blood was obtained at the moment of the administration and three, six, nine, and twenty-four hours after parenteral injection, and after three and six hours when the vitamin was given orally. In some patients receiving the vitamin orally, only fasting and 6-hour specimens of blood were taken, since our chief object was to determine whether these patients had a normal absorption of vitamin A. The determination of the vitamin was made according to the method described by May, and associates. * F r o m the Babies Hospital and D e p a r t m e n t of Pediatrics, Columbia U n i v e r s i t y College of Physicians a n d Surgeons, New York, N. Y. 9The vitamin preparation used in this study w a s made by Endo Products, Inc., Richmond Hill, N'. Y. This w o r k w a s supported b y the Commonwealth Fund. 191
192
THE JOURNAL OF PEDIATRICS TABLE I.
SERUM VITAMIN A AFTER ORAL fiA)MINIBTRATION FASTING 3 HR. LATER 6 HR. LATER 9 VITAMINA -~ l - - ~ ' ~ I N A CAROTENEI I.U./100 CAROTENE] I.U./100 [CAROTENE I.U./100
AGE
DIAGNOSIS NO. (YR.) 1 Rheumatic fever 8 2 Mdni~re's syndrome 9 3 Poliomyelitis 7 convalescent 4 Rheumatic fever 9 5 Rheumatic fever 6 6 Cerebral tumor 9 7 Upper respiratory 2 infection
7/too c.c.]
c.c.
Iv/lO0e.~!
~0.
10.5 9.6 15.3
122 148 155
Iv/leO o.c.]
9.0 9.0 16.0
770 614
4.4 10.2 8.2 25.2
160 154 140 154
3.7 9.8 7.8 28.2
716 549 840 920
7.8 25.4
a~
310 286
T A B L E II. S E R U M V I T A M I N A A F T E R I N T R A M U S C U L A R INJECTION
FASTING CARO- VITATEN~ MIN A 7/100 I.U./100 NO. 1 2 3 4 5 6 7
C.C.
9.0 8.8 15.6 4.6 12.4 7.8 25.0
C.C.
139 142 155 158 101 180 135
3 HR. LATER CAR0TENE
VITAMIN A
~//100 C.C. 9.0 8.6 16.2 4.4 12.2 8.0 25.4
I.U./100 C.C. 139 140 152 150 99 192 198
6HR. LATER O~kRO- VITATENE C.C.
MIN A I.U./lO0 C.O.
10,6 8.8 15.8 4.2 12.6 8.6 25.8
154 142 156 146 91 178 153
~//100
9 HR, LATER CtARO- VITATENE MIN A
-#100 i.u./100 C.O. 10.0 8.6 15.2 4.8 12.2 7.8 25.8
C.O. 156 148 152
24 HR. L A T B CARDTEN]~
VITAM~ 9
~/100 C.O. 10.6 8.8 15.8 4.8
i.u./100 0.0. 140 " 180 184 152
98 178 158
As shown in Table I, all the patients who received vitamin A by the oral route experienced a marked rise in vitamin level after six hours when, according to May and associates, 4 the vitamin A concentration is at its highest level in the plasma. Table II shows that the vitamin was not utilized at all when given parenterally. In some patients the serum vitamin A concentration was assayed twenty-four hours after parenteral administration. This experiment was based on comparable tests performed in dogs by Clausen, s who found that when vitamin A was given intramuscularly, the highest level was obtained after twelve or twenty-four hours. In all our patients from whom we took blood after twenty-four hours, the vitamin concentration was approximately the same as at the beginning. It is concluded that the parenteral administration of vitamin A fails to raise its concentration in the circulating blood. SUMMARY
A comparison has been made between vitamin A absorption curves following oral and parenteral administration of the vitamin in seven children without digestive symptoms. In all cases the oral administration resulted in normal absorption, while the parenteral administration showed little or no evidence of absorption. REFERENCES 1. 2. 8. 4.
Andersen, D. H.: Am. J. Dist. Child 56: 344, 1938. Andersen, D. H.: J. PEDIAT. 15: 763, 1939. Clausen, S. W. : The Harvey Lectures 38: 199, 1943. May, C. D., Blackfan, K. D., McCreary, J. P., and Allen, F. H.: 1167, 1940.
Am. J. Dis. Child 59: