(±)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid,2-amino-2-(hydroxymethyl)-1,3-propanediol

Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the S-form having analgesic

activity.

Binding and Distribution
The Ketorolac tromethamine racemate has been shown to be highly protein bound (99%). Nevertheless, even plasma

concentrations as high as 10 mcg/mL will only occupy approximately 5% of the albumin binding sites. Thus, the unbound

fraction for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will

result in increased free drug concentrations.

The mean apparent volume (Vß) of Ketorolac tromethamine following complete distribution was approximately 13 liters.

This parameter was determined from single-dose data.

Metabolism
Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated

forms of the parent drug. The products of metabolism, and some unchanged drug, are excreted in the urine.

Clearance and Excretion
A single-dose study with 10 mg Ketorolac demonstrated that the S-enantiomer is cleared approximately two times faster than the R-enantiomer and that the clearance was independent of the route of administration. The half-life of the Ketorolac tromethamine S-enantiomer was approximately 2.5 hours (SD ± 0.4) compared with 5 hours (SD ± 1.7) for the R-enantiomer. In other studies, the half-life for the racemate has been reported to lie within the range of 5 to 6 hours.

Accumulation
Steady state was approached after the fourth dose.

Accumulation of Ketorolac tromethamine has not been studied in special populations (elderly patients, renal failure

patients or hepatic disease patients).

Ketorolac is highly bound to human plasma protein (mean 99.2%).
Thein vitro binding ofwarfarin to plasma proteins is only slightly reduced by Ketorolac tromethamine (99.5% control vs.

99.3%).

Ketorolac Tromethamine Injection reduced the diuretic response to furosemide in normo-volemic healthy subjects by

approximately 20% (mean sodium and urinary output decreased 17%).

Concomitant administration of Ketorolac tromethamine tablets and probenecid resulted in decreased clearance of

Ketorolac and significant increases in Ketorolac plasma levels (total AUC increased approximately three-fold from 5.4 to

17.8 mcg/h/mL) and terminal half-life increased approximately two-fold from 6.6 to 15.1 hours. Therefore, concomitant

use of Ketorolac tromethamine and probenecid is contraindicated.

Inhibition of renal lithiumclearance, leading to an increase in plasma lithium concentration, has been reported with some

prostaglandin synthesis-inhibiting drugs. The effect of Ketorolac tromethamine on plasma lithium has not been studied, but

cases of increased lithium plasma levels during Ketorolac tromethamine therapy have been reported.

Concomitant administration of methotrexateand some NSAIDs has been reported to reduce the clearance of

methotrexate, enhancing the toxicity of methotrexate. The effect of Ketorolac tromethamine on methotrexate clearance

has not been studied.

In postmarketing experience there have been reports of a possible interaction between Ketorolac Tromethamine Injection

andnondepolarizing muscle relaxants that resulted in apnea. The concurrent use of Ketorolac tromethamine with muscle

relaxants has not been formally studied.

Concomitant use of ACE inhibitors may increase the risk of renal impairment, particularly in volume-depleted patients.

Sporadic cases of seizures have been reported during concomitant use of Ketorolac tromethamine and antiepileptic drugs

(phenytoin, carbamazepine).

Hallucinations have been reported when Ketorolac tromethamine was used in patients taking psychoactive drugs

(fluoxetine, thiothixene, alprazolam).

Ketorolac Tromethamine Injection has been administered concurrently withmorphine in several clinical trials of

postoperative pain without evidence of adverse interactions. Do not mix Ketorolac tromethamine and morphine in the

same syringe.

1.不得使用於活動性胃潰瘍患者。

2.禁用於嚴重腎功能不全患者及授乳婦。

3.曾對Aspirin、 NSAIDs有過敏反應者禁用。

1.肝功能受損或肝病患者應小心使用。

2.本藥具抑制血小板凝集可能延長出血時間故禁用於手術前給藥當 緊急止血時須小心使用。