Hep C Discussion Forum

Members Login
Username 
 
Password 
    Remember Me  
Chatbox
Please log in to join the chat!
Hep C Discussion Forum -> General Discussion -> Pharmacokinetics - of Harvoni What is it & Why we should care
Post Info TOPIC: Pharmacokinetics - of Harvoni What is it & Why we should care
Matt Chris


Guru

Status: Offline
Posts: 1782
Date:
Pharmacokinetics - of Harvoni What is it & Why we should care
Permalink  
 

 Distribution

Ledipasvir is >99.8% bound to human plasma proteins. After a single 90 mg dose of [14C]-ledipasvir in healthy subjects, the blood to plasma ratio of 14C-radioactivity ranged between 0.51 and 0.66.

Sofosbuvir is approximately 6165% bound to human plasma proteins and the binding is independent of drug concentration over the range of 1 g/mL to 20 g/mL. Protein binding of GS-331007 was minimal in human plasma. After a single 400 mg dose of [14C]-sofosbuvir in healthy subjects, the blood to plasma ratio of 14C-radioactivity was approximately 0.7.

Metabolism

In vitro, no detectable metabolism of ledipasvir was observed by human CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Evidence of slow oxidative metabolism via an unknown mechanism has been observed. Following a single dose of 90 mg [14C]-ledipasvir, systemic exposure was almost exclusively to the parent drug (>98%). Unchanged ledipasvir is the major species present in feces.

Sofosbuvir is extensively metabolized in the liver to form the pharmacologically active nucleoside analog triphosphate GS-461203. The metabolic activation pathway involves sequential hydrolysis of the carboxyl ester moiety catalyzed by human cathepsin A (CatA) or carboxylesterase 1 (CES1) and phosphoramidate cleavage by histidine triad nucleotide-binding protein 1 (HINT1) followed by phosphorylation by the pyrimidine nucleotide biosynthesis pathway. Dephosphorylation results in the formation of nucleoside metabolite GS-331007 that cannot be efficiently rephosphorylated and lacks anti-HCV activity in vitro. After a single 400 mg oral dose of [14C]-sofosbuvir, GS-331007 accounted for approximately >90% of total systemic exposure.

 



__________________

"And in the end, the love you take is equal to the love you make"

61 year old Geno type A1, F4 Cirrhotic, started 24 weeks on Harvoni 12-17-14 ,EOT-5 week = UND, 8-31-15 =UND , SVR-24 Baby YES! 
Matt Chris


Guru

Status: Offline
Posts: 1782
Date:
Permalink  
 

Pharmacokinetics - of Harvoni

Sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body the time course of its absorption, bioavailability, distribution to tissues, and metabolism.

Why it can be important.  Working in harmony with the HCV drugs protocol can make the difference between receiving good results and not so good. Understanding the reason why we should or not eat food with dosing your medicine, sometimes the timing that works with your schedule. This is but a few of the many things that Pharmacokinetics can explain, here is a few more about Harvoni with more to come.

Harvoni -- Pharmacokinetics

Absorption

The pharmacokinetic properties of ledipasvir, sofosbuvir and the predominant circulating metabolite GS-331007 have been evaluated in healthy adult subjects and in patients with chronic hepatitis C. Following oral administration of HARVONI, ledipasvir median peak concentrations were observed 4.0 to 4.5 hours post-dose. Sofosbuvir was absorbed quickly and the peak median plasma concentration was observed ~ 0.8 to 1 hour post-dose. Median peak plasma concentration of GS-331007 was observed between 3.5 to 4 hours post-dose.

Effects of Food

The response rates in Phase 3 trials were similar in HCV-infected patients who received HARVONI with food or without food. Relative to fasting conditions, the administration of a single dose of HARVONI with a moderate fat (~600 kcal, 25% to 30% fat) or high fat (~1000 kcal, 50% fat) meal did not alter the exposures of ledipasvir or GS-331007. Either meal type did not substantially affect the sofosbuvir Cmax and AUCinf. HARVONI can be administered without regard to food.

matt



__________________

"And in the end, the love you take is equal to the love you make"

61 year old Geno type A1, F4 Cirrhotic, started 24 weeks on Harvoni 12-17-14 ,EOT-5 week = UND, 8-31-15 =UND , SVR-24 Baby YES! 
Page 1 of 1  sorted by
 
Quick Reply

Please log in to post quick replies.
Hep C Discussion Forum -> General Discussion -> Pharmacokinetics - of Harvoni What is it & Why we should care
Legal Disclaimer:

THIS FORUM, IT'S OWNERS, ADMINISTRATORS, MODERATORS AND MEMBERS DO NOT AT ANY TIME GIVE MEDICAL ADVICE AND IN ALL CASES REFER ANYONE HERE TO SEEK APPROPRIATE MEDICAL ADVICE FROM THEIR DOCTOR.