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| Primary information |
|---|
| ID | 10874 |
| Therapeutic ID | Th1234 |
| Protein Name | Protamine sulfate |
| Sequence | NA
|
| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Without heparin in healthy individuals: Median 7.4 minutes. With heparin: Median 4.5 minutes. |
| Description | Protamine sulfate is a drug that reverses the anticoagulant effects of heparin by binding to it. It was originally isolated from the sperm of salmon and other species of fish but is now produced primarily through recombinant biotechnology. Protamine sulfate was approved for medical use in the United States in 1969. Protamine sulfate (protamine (protamines) s) occurs as fine white or off-white amorphous or crystalline powder. It is sparingly soluble in water. The pH is between 6 and 7. The cationic hydrogenated protamine at a pH of 6.8 to 7.1 reacts with anionic heparin at a pH of 5.0 to 7.5 to form an inactive complex. |
| Indication/Disease | Protamine sulfate is usually administered to reverse the large dose of heparin administered during certain surgeries, especially heart surgery. |
| Pharmacodynamics | Protamine sulphate 1% demonstrates activity neutralising anticoagulant properties of heparin, creating the complex heparin/protamine. Activity of protamine (towards heparin) takes place within five minutes after intravenous injection of the preparation. |
| Mechanism of Action | It is a highly cationic peptide that binds to either heparin or low molecular weight heparin (LMWH) to form a stable ion pair, which does not have anticoagulant activity. The ionic complex is then removed and broken down by the reticuloendothelial system. In large doses, protamine sulfate may also have an independentâ€â€however weakâ€â€anticoagulant effect. |
| Toxicity | Administration of protamine sulfate intravenously could result in severe drop in blood pressure, dyspnea, bradycardia, pulmonary hypertension and anaphylaxis [F3559, F3562, L5371, L5443]. Systemic hypertension, nausea, vomiting and lassitude were also reported [F3559, F3562, L5371, L5443]. Overdosage of this drug may theoretically result in hemorrhage [F3559, F3562, L5371, L5443]. Nevertheless, any possible carcinogenicity, mutagenicity, effects upon pregnancy, effects on the newborn, on children, elderly individuals and a few other groups at risk have revealed there to be no animal toxicology cited in the literature to indicate that any of these risk factors might be present for protamine sulfate [F3562]. |
| Metabolism | The metabolic fate of the inactive heparin-protamine complex has not yet been formally elucidated [F3559, F3562, L5371, L5443]. Nevertheless, considering protamine sulfate is itself objectively a mixture of basic protein peptide sulfates prepared from sperm or roe of appropriate species of fish (typically of the families Clupeidae or Salmonidae), the involvement of basic protein catalysis via the participation of endogenous peptidases may presumably play a part in the metabolism of protamine sulfate [F3562]. Moreover, as protamine sulfate specifically reverses the anticoagulant activities of heparin by complexing with it, it has also been proposed that the heparin-protamine complex may be plausibly metabolized in part by the lytic enzyme fibrinolysin - a process which would also free heparin [F3559, L5371, L5443]. |
| Absorption | In general, based on data obtained from protamine sulfate administered in healthy humans the AUC demonstrated during the initial infusion is concave [F3562]. Protamine concentrations were less than the limit of detection after twenty minutes or less, although the onset of action had been reported to appear within thirty to sixty seconds after intravenous administration [F3559, F3562, L5371, L5443] It is, however, generally documented that the neutralization of heparin occurs within five minutes after the intravenous administration of protamine sulfate [F3559, L5371, L5443]. Moreover, protamine concentration-versus-time data appears to be substantially different between men and women, where weight-adjusted protamine sulfate dosing ended up in significantly decreased AUC and substantially greater plasma clearance and volume of distribution at steady state in women as compared to men [F3562]. |
| In a study group of twenty-six patients aged between 26 to 80 years and undergoing a cardiac operation with cardiopulmonary bypass, the volume of distribution of protamine sulfate administered was recorded as being 5.4L (with a range of 0.82 to 34L) [A174952]. |
| Clearance | In a study group of twenty-six patients aged between 26 to 80 years and undergoing a cardiac operation with cardiopulmonary bypass, the clearance of protamine sulfate administered was recorded as being 1.4 L/min (with a range of 0.61 to 3.8 L/min) [A174952]. |
| Categories | Heparin Antagonists, Hematologic Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Coagulation factor X,Antithrombin-III |
| Brand Name | Protamine Sulfate Injection, USP |
| Company | Omega Laboratories Ltd |
| Brand Description | Omega Laboratories Ltd |
| Prescribed For | Protamine Sulfate (protamine (protamines) s) Injection, USP is indicated in the treatment of heparin overdosage. |
| Chemical Name | NA |
| Formulation | Protamine sulfate 10 mg, sodium chloride 9 mg and Water for Injection q.s. Sulfuric acid and/or dibasic sodium phosphate (heptahydrate) may have been added for pH adjustment. |
| Physical Appearance | off-white amorphous or crystalline powder |
| Route of Administration | Intravenous |
| Recommended Dosage | Protamine Sulfate (protamine (protamines) s) Injection,USP should be given by very slow intravenous injection in doses not to exceed 50 mg of protamine sulfate (protamine (protamines) s) in any 10-minute period |
| Contraindication | Protamine sulfate (protamine (protamines) s) is contraindicated in patients who have shown previous intolerance to the drug. |
| Side Effects | Intravenous injections of protamine (protamines) may cause a sudden fall in blood pressure, bradycardia, pulmonary hypertension, dyspnea, or transitory flushing and a feeling of warmth. There have been reports of anaphylaxis that resulted in respiratory embarrassment |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |