Lumbrokinase

Pharmacological Actions
Lumbrokinase exhibits multiple pharmacological effects, primarily centered around its fibrinolytic and antithrombotic properties. The following actions have been identified:

Lumbrokinase directly degrades fibrin, the protein mesh in blood clots, and activates the plasminogen system to produce plasmin, which further dissolves clots.
It inhibits Plasminogen Activator Inhibitor-1 (PAI-1), enhancing the activity of tissue plasminogen activator (t-PA), thus amplifying fibrinolytic effects.
Studies, such as Lumbrokinase Mechanism of Action, confirm its dual action, both direct and indirect, distinguishing it from similar enzymes like nattokinase.

Research suggests Lumbrokinase inhibits platelet aggregation and function, reducing the likelihood of clot formation. This is supported by studies like Lumbrokinase and Platelet Function, which highlight its anticoagulation effects.

It inhibits Toll-like receptor 4 (TLR4) signaling, reducing inflammation, particularly in conditions like myocardial ischemia-reperfusion injury. This is detailed in Lumbrokinase and Myocardial Injury, showing its cardioprotective potential.

Lumbrokinase prevents intra-abdominal adhesion by inhibiting fibroblast migration and adhesive activities via the AP-1/ICAM-1 signaling pathway, as evidenced by Intra-abdominal Adhesion Study.

The timing of these actions' influence is not explicitly detailed in studies, with the half-life (discussed below) providing a general indicator of duration. Further research is needed to quantify onset and duration for each action.
Pharmacokinetics: Half-Life and Bioavailability
Half-Life:

The biological half-life of Lumbrokinase, specifically for the formulation DLBS1033, is approximately 8.6 hours when administered orally, based on a clinical trial in healthy volunteers Clinical Trial on Half-Life. This suggests the enzyme remains active in the body for several hours, supporting its therapeutic use.

Oral absorption is possible, with studies using rat everted gut sacs showing absorption rates of 8.7% at 1.0 mg/ml, 11.5% at 2.0 mg/ml, and 14.7% at 0.5 mg/ml after 2 hours, as measured by fibrinolytic activity Intestinal Absorption Study. MALDI-TOF mass spectrometry confirmed absorption into blood, supporting oral efficacy.
Enteric-coated formulations are commonly used to protect Lumbrokinase from stomach acid, enhancing absorption, as noted in Lumbrokinase Benefits. However, exact bioavailability percentages in humans are not consistently reported, with estimates suggesting around 10-15% based on ex vivo data.

Dosage and Administration
Dosage varies depending on the condition and product formulation, often measured in both mass (mg) and activity units (e.g., fibrinolytic units, FU, or lumbrokinase units, LKU):

Typical Dosage for Chronic Conditions: 20-60 mg per day, as recommended by products like Boluoke® Boluoke Dosage, taken one to three times daily on an empty stomach.
Higher Doses for Severe Conditions: Up to 120 mg per day, with clinical trials for acute ischemic stroke using 600,000 units three times a day (total 1,800,000 units per day), as seen in LUCENT Trial Protocol. The activity per mg varies by product, complicating direct comparisons.
Children: Therapeutic dose is 1 capsule per 8 kg body weight per day, according to manufacturer guidelines.

Safety, Toxicity, and Adverse Events
Lumbrokinase is generally considered safe, with a low incidence of adverse events reported in clinical trials:

Safety Profile: A large trial involving 1,560 patients reported a 1.92% adverse reaction rate, including 0.58% skin itching, 0.19% skin rash, and 1.15% nausea or diarrhea, with no major hemorrhages Boluoke FAQ.
Common Side Effects: Gastrointestinal discomfort (nausea, vomiting, diarrhea, stomach cramps), allergic reactions (rash, itching, swelling, dizziness, difficulty breathing), and mild headaches, as detailed in Side Effects Article.
Risks and Contraindications: Increased bleeding risk, especially with anticoagulants or in bleeding disorders. Contraindicated in recent surgery, trauma, active internal bleeding, GI ulceration, or high-risk aneurysm. Caution advised for liver/kidney conditions and pregnant/breastfeeding women.
Toxicity and LD50: Specific LD50 data is not available, and toxic doses are not well-defined. The primary concern is excessive bleeding at high doses, particularly in susceptible individuals, with no reported cases of overdose leading to lethality in reviewed studies.