Melaleuca alternifolia Concentrate (MAC) dengan kandungan kimia terpinen-4-ol mempunyai aktivitas sebagai antiinflamasi dan antimikroba. Studi in vitro menyebutkan bahwa MAC mempunyai kemampuan membunuh virus DV- 1, 2, 3 and 4. Studi keamanan menyebutkan MAC 10 % adalah senyawa yang tidak toksik, dengan nilai LD50 peroral pada tikus dan kelinci adalah 15 dan 21 g/kg bb. Studi farmakokinetik pada ayam ditemukan terpinen-4-ol mencapai puncak pada menit ke-15 dengan kadar (Cmaks 0,04 μg/mL plasma). Sediaan ini berpotensi dikembangkan menjadi fitofarmaka sebagai antivirus dengue, sehingga perlu diteliti profil farmakokinetik pada subyek manusia sehat. Uji dilakukan pada 29 subyek (15 orang laki-laki dan 14 orang wanita) yang memenuhi kriteria inklusi dan eksklusi yang ditetapkan. Uji dilaksanakan di RSUP. Dr. Sardjito Yogyakarta. Subyek secara acak dikelompokkan menjadi 3 kelompok, (I) kelompok dosis tunggal 300 mg, (II) kelompok dosis tunggal 600 mg dan (III) kelompok dosis berulang 300 mg, 3 x sehari selama 5 hari. Penetapan profil farmakokinetik didasarkan pada penetapan kadar terpinen-4-ol dalam serum dan urin dengan metode kromatografi gas detektor FID yang sudah tervalidasi. Terpinen-4-ol dalam MAC sebesar 60% cepat mengalami absorpsi, Cmaks dicapai setelah 1-2 jam pemberian oral dengan kadar 2,84 ng/mL (MAC 300 mg) dan 5,15 ng/mL (MAC 600 mg). Senyawa ini didistribusi secara luas dalam tubuh. Kecepatan eliminasi bervariasi ditunjukkan dengan harga t1/2 eliminasi berkisar antara 28,5-41,6 jam. Ekskresi dalam urin dengan kecepatan 177,78 ng/jam dan 141,67 ng/jam setelah pemberian MAC 300 dan 600 mg. Kadar tunak pemberian berulang (3 x sehari MAC 300 mg, selama 5 hari) tercapai pada kadar 2,72 ng/mL dengan rentang kadar 2,43–2,95 ng/mL).

Melaleuca alternifolia Concentrate (MAC) has been reported to contain mainly terpinen-4-ol, have an anti-inflammatory and antimicrobial In vitro studies found that MAC can inhibit the growth of DV 1, 2, 3 and 4 and ultimately kill the virus. Solution of 10% MAC has also been found to have oral LD50 values found in rats and rabbits are 21 and 15.6 g/kg, respectively which are classified as practically non-toxic. Pharmacokinetic in chicken have been found that Cmaks reach in 0,04 μg/mL plasma). The ultimate objective of the studies is to develop a standardized MAC preparation which contains a major active component terpinen-4-ol (60%) to be a phytopharmaca for the treatment of patients with dengue viral infection. The study involves 29 healthy subjects (15 males and 14 females) who have fulfilled the inclusion criteria, and was done at Dr Sardjito Hospital, Yogyakarta folowing an ethical clearance release by the Faculty of Medicine, Gadjah Mada University. The subjects were allocated randomly into 3 groups of dose regimens of MAC capsules for dose safety studies (ie a single oral dose of 300 mg and 600 mg, and multiple oral doses of 300 mg, 3-times a day for 5 days. The determination of its major, active component (terpinen-4-ol) in serum and urine was done by a validated GC-FID method. Terpinen-4-ol in MAC is rapidly absorbed from the GI tract, and achieved satisfactory concentration in serum 15 minutes after ingestion, and maximum concentrations of 2.84 ng/ml (300 mg dose) and 5.15 ng/ml (600 mg dose) after 1- 2 hours of ingestion. Terpinen-4-ol is also widely distributed in the body with a slow elimination rate with elimination half-lives vary from 28.5 to 41.6 hours. Mean steady-state serum concentration of the compound after 300 mg MAC (3- times/day for 5 days) is 2.72 ng/ml (2.43 to 2.95 ng/ml). Terpinen-4-ol is slowly excreted into urine with average excretion rates of 177.78 ng/hour and 118.49 ng/hour after single oral doses of 300 mg and 600 mg, respectively.

Kata Kunci : Farmakokinetik,Melaleuca alternifolia concentrate (MAC),Terpinen,4,ol, pharmacokinetics, Melaleuca alternifolia Concentrate (MAC), terpinen-4-ol