Famciclovir

321.33

321.33

1312995-182-4

QIC03ANI02

758921

DTXSID0023038

C29044

White shiny plates from ethyl acetate-hexane

J - Antiinfectives for systemic use|S - Sensory organs

29335990

122

0

Solid

1.40±0.1 g/cm3(Predicted)

102-104 °C

550.2±60.0 °C(Predicted)

286.6±32.9 °C

1.628

DMSO: ≥10mg/mL

-20°C Freezer

1.13X10-9 mm Hg at 25 deg C (est)

Henry's Law constant = 9.35X10-14 atm-cu m/mol at 25 °C (est)

pKa1 = 2.91; pKa2 = 3.83 (est)

168.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

NONH for all modes of transport

3

20/21/22-45-61

36/37/39-45-53-24/25

TY3164000

T

P201, P202, P264, P280, P281, P305+P351+P338, P308+P313, P337+P313, P405, P501

H319

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Dispose of waste in accordance with all applicable Federal, State and local laws.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including famciclovir, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H319 (50%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P201, P202, P264, P280, P281, P305+P351+P338, P308+P313, P337+P313, P405, and P501|Aggregated GHS information provided by 4 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Airborne exposure should be controlled primarily by engineering controls such as general dilution ventilation, local exhaust ventilation, or process enclosure. Local exhaust ventilation is generally preferred to general exhaust because it can control the contaminant at its source, preventing dispersion into the work area. An industrial hygiene survey involving air monitoring may be used to determine the effectiveness of engineering controls. Effectiveness of engineering controls intended for use with highly potent materials should be assessed by use of nontoxic surrogate materials. Local exhaust ventilation such as a laboratory fume hood or other vented enclosure is recommended, particularly for grinding, crushing, weighing, or other dust-generating procedures.|Respiratory Protection: Where respirators are deemed necessary to reduce or control occupational exposures, use NIOSH-approved respiratory protection and have an effective respirator program in place. Gloves: Chemically compatible. For handling solutions, ensure that the glove material is protective against the solvent being used. Use handling practices that minimize direct hand contact. Employees who are sensitive to natural rubber (latex) should use nitrile or other synthetic nonlatex gloves. Use of powdered latex gloves should be avoided due to the risk of latex allergy. Eye Protection: Safety glasses with sideshields are recommended. Face shields or goggles may be required if splash potential exists or if corrosive materials are present. Approved eye protection (e.g., bearing the ANSI Z87 or CSA stamp) is preferred. Maintain eyewash facilities in the work area. Protective Clothing: For handling of laboratory scale quantities, a cloth lab coat is recommended. Where significant quantities are handled, work clothing may be necessary to prevent take-home contamination.|Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

This material is assumed to be combustible.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

Avoid exposure to heat and moisture.|As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Clean equipment and work surfaces with suitable detergent or solvent after use. After removing gloves, wash hands and other exposed skin thoroughly.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

If breathed in, move person into fresh air. If not breathing, give artificial respiration.|In case of skin contact, wash off with soap and plenty of water.|In case of eye contact, flush eyes with water as a precaution.|If swallowed, never give anything by mouth to an unconscious person. Rinse mouth with water.

Antiviral drugs have been recently recognized as one of the emerging contaminants in the environment. These are discharged after therapeutic use through human excretion. Effluent containing high concentration of antiviral drugs discharged from production facilities is also a cause of concern to nearby aquatic bodies. There is an increased interest in their removal because they are highly bioactive. Some antiviral drugs are resistant to conventional methods of degradation, and there is a risk of development of antiviral resistance in humans and animals if exposed repeatedly for long periods. To date, the potential human, animal, and ecological risks associated with the discharge of these antiviral compounds to the environment are not well documented. This study presents a brief summary on occurrence, ecotoxicological risks, and physicochemical properties of antiviral drugs in the environment. The needs regarding removal, disposal, and treatment of antiviral drugs are also addressed(1). /Antiviral drugs/

Symptoms of overdose include constipation, diarrhea, dizziness, fatigue, fever, headache, nausea, and vomiting.

Famciclovir has been associated with a low rate of serum aminotransferase elevations during oral therapy. In pooled analyses of patients on long term suppressive therapy, 3.2% of famciclovir vs 1.5% of placebo recipients had ALT elevations above twice normal. The elevations were transient and asymptomatic and resolved even without dose modification. Since approval, cases of cholestatic jaundice have been reported to the sponsor, but there have been no published cases. Thus, clinically apparent liver disease due to famciclovir must be rare if it occurs at all.

The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase. Interactions with other drugs metabolized by this enzyme and/or inhibiting this enzyme could potentially occur. Clinical interaction studies of famciclovir with cimetidine and promethazine, in vitro inhibitors of aldehyde oxidase, did not show relevant effects on the formation of penciclovir. Raloxifene, a potent aldehyde oxidase inhibitor in vitro, could decrease the formation of penciclovir. However, a clinical drug-drug interaction study to determine the magnitude of interaction between penciclovir and raloxifene has not been conducted.|Potential pharmacokinetic interaction with other drugs metabolized by aldehyde oxidase.|Potential increased plasma penciclovir concentrations when used concomitantly with other drugs eliminated by active renal tubular secretion (e.g., probenecid).

20-25%

Famciclovir's production and administration as an antiviral(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that famciclovir is expected to have moderate mobility in soil(SRC). Volatilization of famciclovir from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.4X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Famciclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that famciclovir is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 9.4X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 0.64(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), famciclovir, which has an estimated vapor pressure of 1.1X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase famciclovir may be removed from the air by wet and dry deposition(SRC). Famciclovir contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

A base-catalyzed second-order hydrolysis rate constant of 0.13 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 2 years and 61 days at pH values of 7 and 8, respectively(1). Famciclovir contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for famciclovir(SRC), using an estimated log Kow of 0.64(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of famciclovir can be estimated to be 330(SRC). According to a classification scheme(2), this estimated Koc value suggests that famciclovir is expected to have moderate mobility in soil.

The Henry's Law constant for famciclovir is estimated as 9.4X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that famciclovir is expected to be essentially nonvolatile from water and moist soil surfaces(2). Famciclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-9 mm Hg(SRC), determined from a fragment constant method(3).

There is no information on whether penciclovir is excreted in human milk after topical administration. However, following oral administration of famciclovir (the oral prodrug of penciclovir) to lactating rats, penciclovir was excreted in breast milk at concentrations higher than those seen in the plasma.

Occupational exposure to famciclovir may occur through inhalation and dermal contact with this compound at workplaces where famciclovir is produced or used. Use data indicate that the general population may be exposed to famciclovir via administration of pharmaceutical products containing famciclovir. (SRC)

For the treatment of acute herpes zoster (shingles). Also for the treatment or suppression of recurrent genital herpes in immunocompetent patients and treatment of recurrent mucocutaneous herpes simplex infections in HIV infected patients.|FDA Label

Famciclovir is a nucleoside analogue and antiviral agent used in therapy of herpes zoster and simplex virus infections. Famciclovir is associated with a low rate of mild-to-moderate serum ALT elevations during therapy, but has not been associated with instances of clinically apparent liver injury.

Antiviral Agents

Antiviral Agents|Oral famciclovir is used for the treatment of acute, localized herpes zoster (shingles, zoster). /Included in US product label/|Oral famciclovir is used for the treatment of recurrent mucocutaneous herpes simplex virus (HSV) infections (HSV-1 and HSV-2) in HIV-infected adults. /Included in US product label/|Famciclovir has been used for the management of chronic hepatitis B virus (HBV) infection in a limited number of patients. /NOT included in US product label/|For more Therapeutic Uses (Complete) data for Famciclovir (12 total), please visit the HSDB record page.

/These/ adverse events have been reported during post-approval use of Famvir. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Blood and lymphatic system disorders: Thrombocytopenia. Hepatobiliary disorders: Abnormal liver function tests, cholestatic jaundice. Nervous system disorders: Dizziness, somnolence. Psychiatric disorders: Confusion (including delirium, disorientation, and confusional state occurring predominantly in the elderly), hallucinations. Skin and subcutaneous tissue disorders: Urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema (e.g. face, eyelid, periorbital, and pharyngeal edema).|The manufacturer recommends that the dosage interval of famciclovir be adjusted carefully in patients with impaired renal function to prevent drug accumulation while maintaining adequate plasma concentrations of penciclovir, the active metabolite of famciclovir.|Increased serum concentrations of ALT (SGPT) occurred in 1.4-2.4% of patients receiving famciclovir in clinical trials for herpes zoster or genital herpes. Increased serum concentrations of alkaline phosphatase, total bilirubin, and albumin each occurred rarely in patients receiving the drug in clinical trials for herpes zoster or genital herpes.|The most frequent adverse GI effect of famciclovir is nausea which occurred in approximately 13% of patients receiving the drug (versus in 11.6% in placebo recipients) in a large, controlled clinical trial for herpes zoster. Nausea resulted in discontinuance of famciclovir in less than 1% of patients in clinical trials for herpes zoster or genital herpes. Diarrhea was reported in approximately 8% of patients (5% of placebo recipients) and vomiting in approximately 5% of patients (3.4% of placebo recipients) in a large, controlled clinical trial for herpes zoster. Vomiting only rarely resulted in discontinuance of famciclovir in clinical trials for herpes zoster or genital herpes. Constipation, anorexia, abdominal pain, flatulence, and dyspepsia have occurred in patients receiving famciclovir in clinical trials for herpes zoster. Acute necroticohemorrhagic pancreatitis resulting in death has been reported following famciclovir administration for severe hepatitis B virus infection in a kidney graft recipient who was receiving cyclosporine concomitantly; a causal relationship to famciclovir was not established. Nausea, diarrhea, vomiting, or abdominal pain has been reported in 11, 7, 5, or 3%, respectively, of HIV-infected patients receiving famciclovir in clinical studies.|For more Drug Warnings (Complete) data for Famciclovir (12 total), please visit the HSDB record page.

Famciclovir is a prodrug that undergoes rapid biotransformation to the active antiviral compound penciclovir. Penciclovir is an anti-viral drug which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). Therefore, herpes viral DNA synthesis and replication are selectively inhibited.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Compounds that inhibit cell production of DNA or RNA. (See all compounds classified as Nucleic Acid Synthesis Inhibitors.)

77 %|Active tubular secretion contributes to the renal elimination of penciclovir.|1.08±0.17 L/kg [healthy male subjects following a single intravenous dose of penciclovir at 400 mg administered as a 1-hour intravenous infusion]|36.6 +/- 6.3 L/hr [healthy male]|Following oral administration of famciclovir to lactating rats, penciclovir was distributed into breast milk at concentrations higher than those observed in plasma.|Not known whether penciclovir crosses the placenta or is distributed into human milk.|Following oral single-dose administration of 500 mg famciclovir to seven patients with herpes zoster, the AUC (mean + or - SD), Cmax, and tmax were 12.1+ or - 1.7 ug hr/mL, 4.0 + or - 0.7 ug/mL, and 0.7 + or - 0.2 hours, respectively. The AUC of penciclovir was approximately 35% greater in patients with herpes zoster as compared to healthy volunteers. Some of this difference may be due to differences in renal function between the two groups.|Renal clearance of penciclovir following the oral administration of a single 500 mg dose of famciclovir to 109 healthy male volunteers was 27.7+ or - 7.6 L/hr. Active tubular secretion contributes to the renal elimination of penciclovir.|For more Absorption, Distribution and Excretion (Complete) data for Famciclovir (11 total), please visit the HSDB record page.

Hepatic|Famciclovir is deacetylated and oxidized to penciclovir. Penciclovir is phosphorylated to penciclovir triphosphate (the active metabolite) in cells infected with HSV-1, HSV-2, or VZV. The inactive metabolite 6-deoxy penciclovir is converted to penciclovir by aldehyde oxidase. Famciclovir not metabolized by CYP enzymes.|Following oral administration, famciclovir is deacetylated and oxidized to form penciclovir. Metabolites that are inactive include 6-deoxy penciclovir, monoacetylated penciclovir, and 6-deoxy monoacetylated penciclovir (5%, <0.5% and <0.5% of the dose in the urine, respectively). Little or no famciclovir is detected in plasma or urine. An in vitro study using human liver microsomes demonstrated that cytochrome P450 does not play an important role in famciclovir metabolism. The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase.

10 hours|Elimination half-life of penciclovir after oral administration of famciclovir 1.6-3 hours. Intracellular half-life of penciclovir triphosphate in cells infected with herpes simplex virus (HSV)-1 or HSV-2 is 10 and 20 hours, respectively; intracellular half-life in varicella zoster virus (VZV)-infected cells is 7-14 hours.|The plasma elimination half-life of penciclovir was 2.0 + or - 0.3 hours after intravenous administration of penciclovir to 48 healthy male volunteers and 2.3 + or - 0.4 hours after oral administration of 500 mg famciclovir to 124 healthy male volunteers. The half-life in 17 patients with herpes zoster was 2.8 + or - 1.0 hours and 2.7 + or - 1.0 hours after single and repeated doses, respectively.

Famciclovir undergoes rapid biotransformation to the active antiviral compound penciclovir, which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). In cells infected with HSV-1, HSV-2 or VZV, viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted to penciclovir triphosphate by cellular kinases. In vitro studies demonstrate that penciclovir triphosphate inhibits HSV-2 DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited.|Famciclovir is a prodrug of penciclovir, which has demonstrated inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). In cells infected with HSV-1, HSV-2 or VZV, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate. Biochemical studies demonstrate that penciclovir triphosphate inhibits HSV-2 DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Penciclovir triphosphate has an intracellular half-life of 10 hours in HSV-1-, 20 hours in HSV-2- and 7 hours in VZV-infected cells grown in culture. However, the clinical significance of the intracellular half-life is unknown.

Appropriate symptomatic and supportive therapy should be given. Penciclovir is removed by hemodialysis.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|For more Antidote and Emergency Treatment (Complete) data for Famciclovir (7 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ There was no evidence of any clinically significant effects on sperm count, motility or morphology in 2 placebo-controlled clinical trials of Famvir (famciclovir [the oral prodrug of penciclovir], 250 mg b.i.d.; n=66) in immunocompetent men with recurrent genital herpes, when dosing and follow-up were maintained for 18 and 8 weeks, respectively (approximately 2 and 1 spermatogenic cycles in the human).|/CASE REPORTS/ The development of confusion and bradykinesia during famciclovir therapy for herpes zoster is reported in an 80-yr-old woman who received 500 mg of oral famciclovir 2 times/day for 7 days. The patient's pain and lesions improved markedly within 48 hr of the start of famciclovir therapy, but confusion, urinary incontinence, and periods of immobility developed. She was hospitalized and famciclovir was discontinued. By day 3 her mental status had improved but she experienced more pain and famciclovir was resumed at a dose of 250 mg 3 times/day. The neurologist diagnosed famciclovir related encephalopathy and dementia. ...|/CASE REPORTS/ A 67-year-old white female presented to the hospital for evaluation of large, bilateral palpable purpura; coalescing ulcers with central eschars; and small, red violaceous papules on her legs and groin. Approximately 2 months prior to this hospitalization, the woman was diagnosed with shingles of her left T1-T2 nerve distribution and was treated with famciclovir 500 mg 3 times daily, which was her first exposure to this medication. Her shingles resolved; however, on day 4 of treatment, she began to notice red spots on both of her legs that began to progressively blister and increase in size. She discontinued famciclovir at that time. The rash persisted and spread to her abdomen, groin, legs, feet, and toes. She underwent punch biopsy that revealed leukocytoclastic vasculitis (LCV). Workup was negative for antinuclear antibody, rheumatoid factor, hepatitis B and C virus, perinuclear-staining antineutrophil cytoplasmic antibodies, cytoplasmic-staining antineutrophil cytoplasmic antibodies, antibodies to extractable nuclear antigens, proteinase 3, and myeloperoxidase. The patient improved with daily oral steroids and local wound care. ... The most common cause of LCV is medication use, but it is a diagnosis of exclusion. It is hypothesized that drugs act as haptens, which cause an immune response. An objective causality assessment using the Naranjo probability scale suggested that famciclovir was the probable cause of LCV in this patient.|/GENOTOXICITY/ Famciclovir caused increases in polyploidy in human lymphocytes in vitro in the absence of chromosomal damage at a concentration of 1200 ug/mL.

1,3-Propanediol, 2-(2-(2-amino-9H-purin-9-yl)ethyl)-, diacetate (ester)

Table: Famciclovir Preparations [Table#8101]|Oravir

Categorized under nucleoside analog groups which inhibit viral DNA polymerase

A rapid, specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the determination of penciclovir in human plasma. The method involved simple, one-step SPE procedure coupled with a C(18) , 75 X 4.mm, 3 um column with a flow-rate of 0.5 mL/min, and acyclovir was used as the internal standard. The Quattro Micro mass spectrometry was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. Using 250 uL plasma, the methods were validated over the concentration range 52.555-6626.181 ng/mL, with a lower limit of quantification of 52.55 ng/mL. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a clinical pharmacokinetic study in human volunteers.|A simple, sensitive and reliable HPLC ion-pairing method with fluorescence detection, was developed for penciclovir determination in plasma and aqueous humor, with a Zorbax SB-aq C18 (100 mmx2.1 mm) column. Plasma samples were treated by solid-phase extraction with Oasis MCX (30 mg) cartridges. Ganciclovir, an antiviral drug structurally related to penciclovir, was used as internal standard (I.S.). Aqueous humor samples were directly injected into the chromatographic system. Separation was performed by a gradient elution with a mobile phase consisting of a mixture of acetonitrile and phosphate buffer 50mM containing 5mM of sodium octanesulfonate, pH 2.0, at a flow rate of 0.3 mL/min. The method was validated and showed good performances in terms of linearity, sensitivity, precision and trueness. Quantification limit was obtained at 0.05 ug/mL for aqueous humor and at 0.1 ug/mL for plasma. Finally, the proposed analytical method was used to measure penciclovir in clinical samples for a pharmacokinetic study, after oral administration of famciclovir.|HPLC determination in plasma and urine.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients