1. Home
  2. Vol 50, No 3 (2018)
  3. Gayatri

A Clinical Trial on Biological Half Life of Bioactive Protein from Lumbricus rubellus, DLBS1033 in Healthy Volunteers

Anggi Gayatri, Nafrialdi Nafrialdi, Rahajuningsih D Setiabudy, Raymond R Tjandrawinata, Andika Rachman, Melva Louisa

Abstract


Background: DLBS1033 is a bioactive protein fraction extracted from Lumbricus rubellus, with fibrinogenolytic, fibrinolytic and anti-aggregation activities reported in an in vitro study. Plasma half-life is an important parameter to calculate its dose. This study was conducted to evaluate the biological half-life of DLBS1033 by measuring serial plasmin-antiplasmin (PAP) complex. PAP complex is a stable and inactive compound as a result of fibrinolysis process. Methods: this was an open-label clinical trial in healthy adult subjects. Subjects were divided into two groups to receive single dose drugs (received 3 x 490 mg) or repeated administration until steady state conditions (3 x 490 mg/day for 3 days). Blood samples for PAP complex measurement were collected at time 0 (before drug administration for single dose group), then at 0.5, 1, 1.5, 2, 3, 6, 8, 10, 12, and 24 hours after drug administration. Safety parameters used in this study were creatinine, prothrombin time (PT), activated partial thromboplastin time (aPTT), SGOT, and SGPT. Results: the biological half-life of DLBS1033 was calculated based on the mean of PAP complex concentration on each time sampling. In single dose group, the highest mean of PAP complex concentration was reached before drug administration. Our result showed that the activity of DLBS1033 could not be determined after single dose administration. In steady state condition, the PAP complex concentration increase in 2 hours after last drug administration. The biological half-life of DLBS1033 was 8.6 hours. There were no significant safety findings on all laboratory parameters and no serious adverse events. Conclusion: it is concluded that the fibrinolytic effects of DLBS1033 can be measured in steady state condition. The biological half-life of DLBS1033 in steady state condition was 8.6 hours. There were no serious adverse events on two groups of subjects.

Keywords


Lumbricus rubellus; fibrinolytic; plasmin-antiplasmin complex; biological half-life; DLBS1033

References


Mihara H, Sumi H, Yoneta T, et al. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Japanese J Physiol. 1991;41:461-72.

Trisina J, Sunardi F, Suhartono MT, Tjandrawinata RR. DLBS1033, a protein extract from Lumbricus rubellus, possesses antithrombotic and thrombolytic activities. J Biomed Biotechnol. 2011;1-19.

Lee CK, Shin JS, Kim BS, Cho IH, Kim YS, Lee EB. Antithrombotic effects by oral administration of novel proteinase fraction from earthworm Eisenia andrei on venous thrombosis model in rats. Arch Pharm Res. 2007; 30:475-80.

Kholos JA. The anti-inflammatory and antiplatelet effects of Boluoke (Lumbrokinase) in cancer patients. Townsend Lett. 2009:62-6.

Jin L, Jin H, Zhang G, Xu G. Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. Clin Hemorheol Microcirc. 2000;23:2138.

Rey I. Pengaruh pemberian lumbrokinase selama 7 hari terhadap status hiperkoagulasi pada penderita ulkus kaki diabetik. Tugas Akhir Dalam Rangka menyelesaikan Pendidikan Dokter Spesialis Ilmu Penyakit Dalam. FK-USU, Medan. 2009.

Yan XM , Kim CH, Lee CK, Shin JS, Cho IH, Sohn UD. Intestinal absorption of fibrinolytic and proteolytic lumbrokinase extracted from earthworm, Eisenia andrei. Korean J Physiol Pharmacol. 2010;14:71-5.

Oesman F, Setiabudy RD. Fisiologi hemostasis dan fibrinolisis. In: Setiabudy RD, eds. Hemostasis dan trombosis. 4th edition. Jakarta: Balai Penerbit FKUI; 2009. p. 1-14.

Schmaier AH, Thornburg CD, Pipe SW. Coagulation and fibrinolysis. In: McPherson RA, Pincus MR, eds. Henrys clinical diagnosis and management by laboratory methods. 21st ed. Philadelphia: Saunders Elsevier; 2007. p. 729-37.

Bauer KA, Weitz JI. Laboratory markers of coagulation and fibrinolysis. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN, eds. Hemostasis and thrombosis basic principles and clinical practice. 4th ed. Philadelphia: Lippincott Williams & Wilkins. 2001. p. 1113-7.

Brinkman GL, Coates EO Jr: The effect of bronchitis, smoking and occupation on ventilation. Ann Respir Dis. 1963;87:684-93.

Tjandrawinata RR, Trisna J, Rahayu P, Prasetya LA, Hanafiah A, Rachmawati H. Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies. Drug Design, Development Therapy. 2014;8: 1585-93.

Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Brit J Haematol. 2005;129:307-21.

Bouma B, Maas C, Hazenberg BPC, Lokhorst HM, Gebbink FBG. Increased plasmin-?2-antiplasmin level indicate activation of the fibrinolytic system in systemic amyloidosis. J Thromb Haemost. 2007;5: 1139-42.

Kasim M, Kiat AA, Rohman MS, Hanifah Y, Kiat H. Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: A pilot study. J Alternat Complement Med. 2009;15:539-44.


Full Text: PDF

Refbacks

  • There are currently no refbacks.