Serum alkaline phosphatase

The chronic-duration oral MRL was derived based on the observation of increased serum levels of alkaline phosphatase (an indicator of hepatotoxicity) in dogs consuming 0.6 mg/kg/day for 1 year (Hoechst 1989c). The choice of this end point is supported by the observation of hydropic hepatic cells in rats that consumed 5 mg/kg/day for 2 years (EMC 1959b). The chronic-duration MRL of 0.002 mg/kg/day was derived by dividing the NOAEL for elevated serum alkaline phosphatase (0.18 mg/kg/day) by an uncertainty factor of 100 (10 for extrapolating from animals to humans, and 10 for human variability). 

Dose and end point used for MRL derivation 0.18 mg/kg/day for increase in serum alkaline phosphatase activity. 

Alkaline phosphatase assays based on 3-glycerophosphate now appears to be obsolete, and methods buffered by either glycine or barbital are also obsolete as these buffers inhibit ALP or are poor buffers. Serum alkaline phosphatase is known to be composed of several isoenzymes which presumably arise from bone, liver, intestine, and placenta. The placental alkaline phosphatase is known to be much more resistant to heat denaturation than the other isoenzymes, and this resistance provides a simple test for it (5). The other enzymes can be separated through the differential inhibition by phenylalanine, by electrophoresis and by specific antibodies. However, the clinical usefulness of the results obtained is in doubt (23). 

TABLE VI EVOLUTION OF SERUM ALKALINE PHENYL PHOSPHATASE METHODS >... 

The Group II (biliary tract) enzymes are abnormal usually when the serum bilirubin concentration is also abnormal. Most commonly used is alkaline phosphatase which is a highly sensitive indicator of biliary tract obstruction, perhaps because the enzyme is synthesized as an induced response to obstruction of even small bile ducts. Most techniques used to identify the origin of an elevated serum alkaline phosphatase are not very useful from a clinical viewpoint (23). The simultaneous measurement of GMT activity has been found to be useful in differentiating between the hepatic and bony origin of alkaline phosphatase. An increased GMT activity in a patient with an increased ALP activity is a good indication that there is biliary biliary tract disease (62,63). 

Roos, R. A simplified method for the determination of serum alkaline phosphatase activity. Scand. J. Clin. 

Bowers, 6. N., Jr. Kelley, M. L. and McComb, R. B. Precision estimates in clinical chemistry. I. Variability of analytic results in a survey reference sample related to the use of a non-human serum alkaline phosphatase. Clin. Chem. (1967), 14, 595-607. 

Alkaline phosphatase Serum Harp seal Yes Increased Ronald et al. (1977)... 

Increased serum alkaline phosphatase was observed in rats receiving 1,000 mg/kg/day of MIL-H-83282 for 4 weeks but not in rats similarly exposed to 1,000 mg/kg/day MIL-H-83282LT (Mattie et al. 1993). Increased peroxisomal beta-oxidation rates were seen after exposure to both fluids, but the toxicological significance of this finding is unclear (Mattie et al. 1993). 

Hyperproteinemia, hyperglycemia, and enhanced serum alkaline and acid phosphatase activities (WHO 1984)... 

AP may be associated with leukocytosis, hyperglycemia, hypoalbumin-emia, mild hyperbilirubinemia, and elevations in serum alkaline phosphatase and hepatic transaminases. 

Tuba et al. (24) reported that rats fed 15.4% dried rhubarb or an equivalent amount of sodium oxalate grew at a slower rate and had higher serum alkaline phosphatase levels than rats fed control diets containing calcium lactate. The calcium lactate diets contained either 0.5% or 0.09% calcium. The rhubarb and sodium oxalate diets contained 0.5% calcium and 0.95% oxalate. 

Hepatic Effects. An increase in serum alkaline phosphatase was noted in workers exposed to unspecified levels of cyanide however, serum bilirubin was found to be within the normal range in these workers (Kumar et al. 1992). 

Serum alkaline phosphatase elevations have been reported following administration of salt-poor albumin (B5). Placenta is very rich in a heat-stable alkaline phosphatase, and albumin prepared from placental blood has a high activity of this enzyme. In one cirrhotic patient who received 1-6 units per day of albumin obtained from pooled human blood and/or human placenta, the alkaline phosphatase before infusion was 5 Bodansky units and by the thirteenth day of administration had reached a value of 160 units. The physician administering the albumin at first thought the patient was having a severe toxic liver reaction and stopped the therapy. The alkaline phosphatase then started to go down and within 10 days returned to normal levels. Analysis of the albumin indicated that it contained 470 units of alkaline phosphatase activity and was probably responsible for the observed elevations in the serum enzyme activity. Albumin prepared from venous blood did not cause an alkaline phosphatase elevation, but placenta-albumin caused elevations with a half-life of about 8 days (Ml). 

B5. Bark, C. J., Artifactual elevations of serum alkaline phosphatase following... 

Retreatment - Retreatment with alendronate may be considered, following a 6-month posttreatment evaluation period, in patients who have relapsed based on increases in serum alkaline phosphatase. Retreatment also may be considered in those who failed to normalize... 

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