Bioequivalence assessment of Lovrak (Julphar, UAE) compared with Zovirax (Glaxo Wellcome, UK)‐Two brands of Acyclovir‐in healthy human volunteers

Najib, Naji M.; Idkaidek, Nasir; Beshtawi, M.; Mohammed, Baba Sulemana; Admour, Isra'; Alam, S. Mahmood; Dham, Ruwayda; Qumaruzaman,

doi:10.1002/bdd.426

Cited by 8 publications

(13 citation statements)

References 11 publications

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“…Its absorption occurs mainly by passive diffusion mechanism and it is slow, variable and incomplete 23, 55. Maximum plasma concentrations are reached within 1.5–2.5 h 18, 22, 23, 55, 56. Aciclovir shows a two compartment pharmacokinetic behavior, regardless of the dosage, duration of treatment or frequency of administration 36.…”

Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Aciclovir

Arnal

González‐Álvarez

Bermejo

et al. 2008

Journal of Pharmaceutical Sciences

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Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which fall just within BCS Class IV. Aciclovir seems not to be critical with respect to a risk for bioinequivalence, as no examples of bioinequivalence have been identified. It has a wide therapeutic index and is not used for critical indications. Hence, if: (a) the test product contains only excipients present in aciclovir solid oral IR drug products approved in ICH or associated countries, for instance as presented in this article; and (b) the comparator and the test product both are very rapidly dissolving, a biowaiver for IR aciclovir solid oral drug products is considered justified for all tablet strengths.

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Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Aciclovir

Arnal

González‐Álvarez

Bermejo

et al. 2008

Journal of Pharmaceutical Sciences

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“…Because of incomplete and variable absorption of acyclovir, the present study involves development of a newly immediate release oral highest dose (800mg) pharmaceutical formulation used clinically significant in various HSV and VZV infected patients. This study was designed to assess comparative pharmacokinetics, food effects, safety and tolerability of newly developed oral test immediate release formulation with that of a reference product (Zovirax ® , GlaxoSmithKline, Uxbridge, UK) in healthy, male, Indian volunteers under fasting and non-fasting conditions according to ICH guidelines [45,46].…”

Section: Acyclovirmentioning

confidence: 99%

“…To account for subject withdrawal and dropouts due to adverse events, and non-compliance or personal reasons, 36 subjects were selected, randomized and enrolled into the study. Hence a total of 36 subjects were enrolled in the study [45,46].…”

Section: Subject Sample Size Determinationmentioning

confidence: 99%

“…The standard high-fat breakfast meal consists of two slices of toast with two butter pads, 200 mL of whole milk, two butter egg omelet, one chicken cutlet and 100gms of french potato fries. The high-fat breakfast meal provided an estimated 66.2 g of carbohydrates (264.96 Calories and 26.78%), 37.13 g of protein (148.52 Calories and 15.01%), and 63.96 g of fat (575.64 Calories and 58.21%), and total 989.12 Calories, respectively [45,46]. Each subject received a single oral dose of test or reference products with 240 mL of water at room temperature in each period as per randomization schedule and continued fasting for 4 hours in both fasting and nonfasting study.…”

Section: Experimental Designmentioning

confidence: 99%

“…Drinking water was not allowed from one hour before dosing till two hour post-dose (except 240mL of water given for dosing) and before and after that subjects were allowed to ingest water ad libitum. Subjects were received identical, nutritionally balanced standard meals at 4.00, 9.00 and 13.00hours after dosing in each periods of both fasting and non-fasting study [45,46].…”

Section: Experimental Designmentioning

confidence: 99%

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Comparative Pharmacokinetics, Safety and Tolerability Evaluation of Acyclovir IR 800 Mg Tablet in Healthy Indian Adult Volunteers Under Fasting and Non-fasting Conditions

Susantakumar¹,

Gaur²,

Sharma³

2011

JBB

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Objectives: This study was designed to determine the comparative pharmacokinetics, safety and tolerability of test acyclovir 800mg IR formulation with reference product (Zovirax® 800mg IR Tablet) after single dose administration under fasting and non-fasting conditions in 36 male and female adult subjects. Methods: Open label, balanced, randomized, two-sequence, single-dose, two-way crossover study design in healthy Indian adult volunteers with a washout period of at least 7 days was used. Each subject received an acyclovir test or reference product respectively. Blood samples were collected before dosing and at various time points up to 24 hours after dosing. Plasma samples were analyzed by validated liquid chromatography with tandem mass spectrometry method. The pharmacokinetic parameters C max , T max , MRT, AUC 0-t , and AUC 0-∞ were analyzed using non-compartment model. Drug safety and tolerability were assessed. Results: Total 36 and 34 subjects in fasting in non-fasting study had completed both treatment periods. Two subjects were dropout due to family reason. No statistical significance difference of pharmacokinetic parameters C max , AUC 0-t and AUC 0-∞ between test and reference product. Food dose not affects the rate and extent of acyclovir absorption in systemic circulation was observed in both fasting and non-fasting study. The significant sequence (carry-over) effects of AUC 0-t and AUC 0-∞ were acceptable due to non detectable drug in pre-dose samples in analyzed subjects. Total 07 subjects reported 26 adverse events during the fasting study, and 06 subjects reported adverse events during the non-fasting study. Acyclovir was found safe and well tolerated by all subjects who had completed the study in good health conditions. Conclusion: The single dose pharmacokinetics, safety and tolerability study found that the test formulation acyclovir 800mg immediate release tablets were comparable to the reference product at rate and extent of absorption under fasting and non-fasting conditions in healthy adult subjects according to the USFDA regulatory guidance.

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Rapid determination of acyclovir in plasma and cerebrospinal fluid by micellar electrokinetic chromatography with direct sample injection and its clinical application

2006

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A simple MEKC with UV detection at 254 nm for analysis of acyclovir in plasma and in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment is described. The separation of acyclovir from biological matrix was performed at 25 degrees C using a BGE consisting of Tris buffer with SDS as the electrolyte solution. Several parameters affecting the separation of the drug from biological matrix were studied, including the pH and concentrations of the Tris buffer and SDS. Using dyphylline as an internal standard, the linear ranges of the method for the determination of acyclovir in plasma and in CSF all exceeded the range of 2-50 microg/mL; the detection limit of the drug in plasma and in CSF (S/N = 3; injection 3.45 kPa, 5 s) was 1.0 microg/mL. The applicability of the proposed method for determination of acyclovir in plasma and CSF collected at 8 h after intravenous administration of 500 mg acyclovir (Zovirax) in two patients with herpes simplex encephalitis was demonstrated.

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Bioequivalence assessment of Lovrak (Julphar, UAE) compared with Zovirax (Glaxo Wellcome, UK)‐Two brands of Acyclovir‐in healthy human volunteers

Cited by 8 publications

References 11 publications

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Aciclovir

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Aciclovir

Comparative Pharmacokinetics, Safety and Tolerability Evaluation of Acyclovir IR 800 Mg Tablet in Healthy Indian Adult Volunteers Under Fasting and Non-fasting Conditions

Rapid determination of acyclovir in plasma and cerebrospinal fluid by micellar electrokinetic chromatography with direct sample injection and its clinical application

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