Peringatan Keamanan

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.

Protamine sulfate

DB09141

biotech approved

Deskripsi

Since it's earliest discovery in salmon rine sperm heads in the late 1800's to its formal introduction via US FDA approval in 1939, protamine sulfate has occupied an important therapeutic niche as perhaps the only viable option for reversing the anticoagulant effect of heparin use for over 77 years A174778, A174781. Subsequently, because most invasive surgical procedures involve the routine use of heparin to prevent potentially surgery-complicating blood clotting, most cases of major bleeding in these frequent procedures are managed with the use of protamine sulfate A174778. The agent elicits this heparin reversal predominantly via the formation of an inactive complex between the anionic nature of heparin and its own cationic state A174778, A174781, L5371.

Despite the relative importance of protamine sulfate's medical indication, the medication can notoriously cause a variety of potentially rare but genuinely severe adverse effects that include systemic hypotension, pulmonary hypertension, liver and kidney tissue damage, and anaphylactic reaction, amongst others A174778, L5371. As a consequence, whenever protamine sulfate use is clinically considered, careful consideration must be given as to whether the use of the agent could decrease the safety of the procedure or worsen the recovery of a patient after the procedure A174778, A174781, L5371.

Regardless, protamine sulfate continues to see contemporary use given its genuine effectiveness in reversing heparin effects. Although current up to date reviews and studies continue to search for new therapeutic alternatives to protamine sulfate, most substitutes possess similar and unacceptable adverse effects A174778, A174781. Of the few agents that may be considered potentially successful alternatives - including idarucizumab for dabigatran reversal - their cost of procurement and potential range in reversing all parenteral anticoagulants are sometimes considered high and limited, respectively A174778, A174781.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The half-life of protamine sulfate in healthy individual volunteers without heparin in the body was determined to be about a median 7.4 minutes (from a range of 5.9-9.3 minutes) [A174952]. For surgical patients undergoing a cardiac operation with cardiopulmonary bypass with the use/presence of heparin in the body, the half-life recorded was a median 4.5 minutes (from a range of 1.9-18 minutes) [A174952].
Volume Distribusi 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].
Klirens (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].

Absorpsi

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.

Metabolisme

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.

Rute Eliminasi

Data from limited studies regarding the elimination of protamine sulfate from the human body have determined that protamine excretion is predominantly renal A174982.

Interaksi Obat

0 Data
Tidak ada data.

Referensi & Sumber

Artikel (PubMed)
  • PMID: 27223896
    Sokolowska E, Kalaska B, Miklosz J, Mogielnicki A: The toxicology of heparin reversal with protamine: past, present and future. Expert Opin Drug Metab Toxicol. 2016 Aug;12(8):897-909. doi: 10.1080/17425255.2016.1194395. Epub 2016 Jun 6.
  • PMID: 24019031
    Bromfield SM, Wilde E, Smith DK: Heparin sensing and binding - taking supramolecular chemistry towards clinical applications. Chem Soc Rev. 2013 Dec 7;42(23):9184-95. doi: 10.1039/c3cs60278h. Epub 2013 Sep 10.
  • PMID: 12440613
    Butterworth J, Lin YA, Prielipp RC, Bennett J, Hammon JW, James RL: Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass. Ann Thorac Surg. 2002 Nov;74(5):1589-95.
  • PMID: 8268631
    DeLucia A 3rd, Wakefield TW, Kadell AM, Wrobleski SK, VanDort M, Stanley JC: Tissue distribution, circulating half-life, and excretion of intravenously administered protamine sulfate. ASAIO J. 1993 Jul-Sep;39(3):M715-8.

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