PMID- 32472357
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20210702
IS  - 2107-0180 (Electronic)
IS  - 0378-7966 (Linking)
VI  - 45
IP  - 5
DP  - 2020 Oct
TI  - Bioequivalence and Tolerability of Ambrisentan: A Pharmacokinetic Study in 
      Mexican Healthy Male Subjects.
PG  - 611-618
LID - 10.1007/s13318-020-00627-3 [doi]
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a disease characterized by a 
      progressive rise in pulmonary vascular resistance. Ambrisentan is an oral, 
      propanoic acid based-endothelin receptor antagonist (ERA), selective for the 
      endothelin type-A receptor, which is approved for the treatment of PAH. The 
      Colombia National Food and Drug Surveillance Institute regulatory criteria 
      require demonstrating that the proposed generic product is bioequivalent to its 
      reference-listed drug to obtain marketing approval. OBJECTIVES: The purpose of 
      this study was to test the bioequivalence, pharmacokinetics, and tolerability of 
      ambrisentan 10 mg tablets. METHODS: In this open-label, randomized, oral 
      single-dose, two-way crossover bioequivalence study, 26 Mexican adult healthy 
      male subjects received either the generic product of ambrisentan 10 mg or the 
      reference product Volibris((R)) (ambrisentan) 10 mg tablets during each study 
      period under fasting conditions. There was a 7-day washout period between each 
      dosing. Ambrisentan concentrations in plasma samples were quantified using a 
      validated ultra-performance liquid chromatography coupled with tandem mass 
      spectrometry (UPLC-MS/MS) method. Blood samples were collected up to 72 h 
      post-dose in each study period. The primary end points were maximum plasma 
      concentration (C(max)) and area under the plasma concentration-time (AUC(0-t)) 
      curve between 0 and 72 h for ambrisentan. RESULTS: The ratios (90% CI) of 
      geometric mean for ambrisentan were 104.3% (97.12-111.98%) and 100.2% 
      (95.56-104.72%). These pharmacokinetic parameter values lie within the 
      INVIMA-specified bioequivalence limits of 80%-125%. Nervous system disorders were 
      the most common adverse events (AEs). All AEs were mild to moderate in nature and 
      were resolved after follow-up or pharmacologic treatment. Both products were safe 
      and well tolerated. CONCLUSIONS: The test product ambrisentan 10 mg tablets is 
      bioequivalent to the reference product Volibris((R)) (ambrisentan) 10 mg tablets. 
      Both treatments were well tolerated in the Mexican male population of this study. 
      TRIAL REGISTRATION: COFEPRIS National Clinical Trials Registry number 
      183300410B0367/2018.
FAU - Cardenas, Karen Paola Camarillo
AU  - Cardenas KPC
AUID- ORCID: 0000-0001-9895-1039
AD  - Avant Sante Research Center S.A. de C.V, San Pedro Garza Garcia, Nuevo Leon, 
      Mexico. kcamarilloc@avantsante.com.
FAU - Velazquez, Joceline Estefania Rangel
AU  - Velazquez JER
AD  - Avant Sante Research Center S.A. de C.V, San Pedro Garza Garcia, Nuevo Leon, 
      Mexico.
FAU - Escobar, Javier Jesus Osorio
AU  - Escobar JJO
AD  - Avant Sante Research Center S.A. de C.V, San Pedro Garza Garcia, Nuevo Leon, 
      Mexico.
FAU - Chirinos, Juan
AU  - Chirinos J
AD  - Abbott Laboratories de Colombia, Bogota, Colombia.
FAU - Pendela, Murali
AU  - Pendela M
AD  - Avant Sante Research Center S.A. de C.V, San Pedro Garza Garcia, Nuevo Leon, 
      Mexico.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - France
TA  - Eur J Drug Metab Pharmacokinet
JT  - European journal of drug metabolism and pharmacokinetics
JID - 7608491
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Drugs, Generic)
RN  - 0 (Phenylpropionates)
RN  - 0 (Pyridazines)
RN  - 0 (Tablets)
RN  - HW6NV07QEC (ambrisentan)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Antihypertensive Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Area Under Curve
MH  - Chromatography, High Pressure Liquid
MH  - Cross-Over Studies
MH  - Drugs, Generic/*administration & dosage/adverse effects/pharmacokinetics
MH  - Humans
MH  - Male
MH  - Mexico
MH  - Phenylpropionates/*administration & dosage/adverse effects/pharmacokinetics
MH  - Pyridazines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Tablets
MH  - Tandem Mass Spectrometry
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2020/05/31 06:00
MHDA- 2021/07/03 06:00
CRDT- 2020/05/31 06:00
PHST- 2020/05/31 06:00 [pubmed]
PHST- 2021/07/03 06:00 [medline]
PHST- 2020/05/31 06:00 [entrez]
AID - 10.1007/s13318-020-00627-3 [pii]
AID - 10.1007/s13318-020-00627-3 [doi]
PST - ppublish
SO  - Eur J Drug Metab Pharmacokinet. 2020 Oct;45(5):611-618. doi: 
      10.1007/s13318-020-00627-3.