Pharmacokinetic Properties of 200 and 400 mg Acyclovir Tablet in Indonesia Healthy Subject

Drug Use Clinical Trial

Official title:

Pharmacokinetic Properties of Acyclovir

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04988646
• Other study ID #: 515/STD/PML/2019
• Status: Completed
• Phase: N/A
• Start date: February 21, 2020
• Est. completion date: April 28, 2020

Study information

• Verified date: February 2023
• Source: PT. Kimia Farma (Persero) Tbk
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this present study was to asses the pharmacokinetic properties of acyclovir tablet from new product formulation (PT. Kimia Farma (Persero) Tbk) to its innovator product, Zovirax® tablet (Glaxo Wellcome S.A., Aranda, Spain)

Description:

Twenty-eight healty subjects were given a single dose of acyclovir tablet or Zovirax® in dosage form 200 mg and 400mg with 240 mL of water. Then the blood samples for acyclovir was drawn and analyzed using LCMS/MS. All subjects sample plasma were analyzed for pharmacokinetic evaluation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: April 28, 2020
• Est. primary completion date: April 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• body weight within normal range (body mass index between 18 and 25 kg/m2)

• had normal blood pressure (systolic was ranged between 90 to 120 mmHg and diastolic was ranged between 60 to 80 mmHg)

• had normal electrocardiogram

• absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening

Exclusion Criteria:

• pregnant women

• nursing mothers

• women of childbearing potential without adequate contraception

• had a history of contraindication or hypersensitivity to aciclovir, or other antiviral or other ingredients in the study products or a history of serious allergic reaction to any drug,

• a significant allergic disease, or allergic reaction; presence of medical condition which might significantly influence the pharmacokinetics of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease

• presence of any coagulation disorder or clinically significant hematology abnormalities; using any medication (prescription or non-prescription drug, food supplement, herbal medicine)

• particularly the medication known to affect the pharmacokinetics of the study drug

• who had participated in any clinical study within 3 months prior to the study (< 90 days)

• subjects who had donated or lost 300 ml (or more) of blood within 3 months prior to the study

• who were positive to HIV, HBsAg, and HCV tests

• who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits

• poor venous access; and who smoked more than 10 cigarettes a day

• had a history of drug or alcohol abuse within 12 months prior to screening for this study and who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits, poor venous access

Related Conditions & MeSH terms

• Drug Use

Intervention

Drug:
• Acyclovir 200 MG
Administered with 240 mL of water
• Acyclovir 400 MG
Administered with 240 mL of water
• Zovirax 200 MG Tablet
Administered with 240 mL of water
• Zovirax 400 MG Tablet
Administered with 240 mL of water

Locations

Country	Name	City	State
Indonesia	PT Pharma Metric Labs	Jakarta Pusat	DKI Jakarta

Sponsors (2)

Lead Sponsor	Collaborator
PT. Kimia Farma (Persero) Tbk	PT Pharma Metric Labs

Country where clinical trial is conducted

Indonesia, 

References & Publications (13)

Ahronowitz I, Fox LP. Herpes zoster in hospitalized adults: Practice gaps, new evidence, and remaining questions. J Am Acad Dermatol. 2018 Jan;78(1):223-230.e3. doi: 10.1016/j.jaad.2017.07.054. Epub 2017 Nov 14. — View Citation

Al-Yamani MJ, Al-Khamis KI, El-Sayed YM, Bawazir SA, Al-Rashood KA, Gouda MW. Comparative bioavailability of two tablet formulations of acyclovir in healthy volunteers. Int J Clin Pharmacol Ther. 1998 Apr;36(4):222-6. — View Citation

Amini H, Javan M, Gazerani P, Ghaffari A, Ahmadiani A. Lack of bioequivalence between two aciclovir tablets in healthy subjects. Clin Drug Investig. 2008;28(1):47-53. doi: 10.2165/00044011-200828010-00006. — View Citation

Corrao G, Soranna D, La Vecchia C, Catapano A, Agabiti-Rosei E, Gensini G, Merlino L, Mancia G. Medication persistence and the use of generic and brand-name blood pressure-lowering agents. J Hypertens. 2014 May;32(5):1146-53; discussion 1153. doi: 10.1097 — View Citation

de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother. 1983 Sep;12 Suppl B:29-37. doi: 10.1093/jac/12.suppl_b.29. — View Citation

Fletcher C, Bean B. Evaluation of oral acyclovir therapy. Drug Intell Clin Pharm. 1985 Jul-Aug;19(7-8):518-24. doi: 10.1177/106002808501900703. — View Citation

Galgatte UC, Jamdade VR, Aute PP, Chaudhari PD. Study on requirements of bioequivalence for registration of pharmaceutical products in USA, Europe and Canada. Saudi Pharm J. 2014 Nov;22(5):391-402. doi: 10.1016/j.jsps.2013.05.001. Epub 2013 May 31. — View Citation

Kesselheim AS, Misono AS, Lee JL, Stedman MR, Brookhart MA, Choudhry NK, Shrank WH. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008 Dec 3;300(21):2514-26. doi: 10.1001/ — View Citation

Kukhanova MK, Korovina AN, Kochetkov SN. Human herpes simplex virus: life cycle and development of inhibitors. Biochemistry (Mosc). 2014 Dec;79(13):1635-52. doi: 10.1134/S0006297914130124. — View Citation

O'Brien JJ, Campoli-Richards DM. Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1989 Mar;37(3):233-309. doi: 10.2165/00003495-198937030-00002. — View Citation

Stahl JP, Mailles A. Herpes simplex virus encephalitis update. Curr Opin Infect Dis. 2019 Jun;32(3):239-243. doi: 10.1097/QCO.0000000000000554. — View Citation

Vaithianathan S, Haidar SH, Zhang X, Jiang W, Avon C, Dowling TC, Shao C, Kane M, Hoag SW, Flasar MH, Ting TY, Polli JE. Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs Cimetidine and Acyclov — View Citation

Weller S, Blum MR, Doucette M, Burnette T, Cederberg DM, de Miranda P, Smiley ML. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993 Dec;54(6):5 — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics Parameter	Maximum plasma concentration (Cmax)	before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing
Primary	Pharmacokinetics Parameter	Area Under Curve from 0 to 24 hours (AUCt)	Predose at (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose
Secondary	Geometric Mean Ratio	The ratio between maximum concentration of test drug and reference drug after drug administration	before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing
Secondary	Geometric Mean Ratio	The ratio between area under curve from 0 to 24 hours of test drug and reference drug	before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing