PMID- 35018553
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220531
IS  - 2107-0180 (Electronic)
IS  - 0378-7966 (Print)
IS  - 0378-7966 (Linking)
VI  - 47
IP  - 2
DP  - 2022 Mar
TI  - A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in 
      Adults with Mild, Moderate, and Severe Renal Impairment.
PG  - 235-245
LID - 10.1007/s13318-021-00747-4 [doi]
AB  - BACKGROUND AND OBJECTIVES: Lorlatinib is approved (100 mg once daily [QD]) for 
      the treatment of patients with anaplastic lymphoma kinase- (ALK) positive 
      metastatic non-small cell lung cancer. This study evaluated the impact of varying 
      degrees of renal impairment on the safety and pharmacokinetics of lorlatinib. 
      METHODS: Participants were assigned to mild, moderate, and severe renal 
      impairment groups and to a matching normal renal function group based on absolute 
      estimated glomerular filtration rate (eGFR, based on the Modification of Diet in 
      Renal Disease equation and adjusted for body surface area [BSA]) and were 
      evaluated for pharmacokinetics and safety. RESULTS: A total of 29 participants (5 
      with severe renal impairment; 8 each with moderate and mild impairment and normal 
      renal function) were enrolled and received a single dose of lorlatinib 100 mg. 
      One of the participants with severe renal impairment had end-stage renal disease 
      with a baseline absolute eGFR of 10.3 mL/min. No serious adverse events (AEs) 
      were reported. Eighteen AEs, all mild or moderate in severity, were reported by 
      12 participants (5, 2, 4, and 1 in the normal, mild, moderate, and severe groups, 
      respectively). Area under the plasma concentration-time profile from time zero 
      extrapolated to infinity (AUC(inf)) for lorlatinib was increased by 4%, 19%, and 
      41% in the mild, moderate, and severe renal impairment groups, respectively, 
      compared with the normal renal function cohort. CONCLUSION: Lorlatinib 100 mg was 
      well tolerated. As participants with mild and moderate renal impairment did not 
      experience clinically meaningful increases in lorlatinib exposure, no lorlatinib 
      dose adjustment is recommended in these populations. Patients with severe renal 
      impairment are recommended to reduce the starting dose of lorlatinib from 100 mg 
      QD to 75 mg QD. GOV IDENTIFIER: NCT03542305 (available May 31, 2018 on 
      clinicaltrials.gov).
CI  - (c) 2022. The Author(s).
FAU - Lin, Swan
AU  - Lin S
AUID- ORCID: 0000-0002-7705-9401
AD  - Pfizer Inc., Global Product Development, San Diego, CA, USA. swandlin@gmail.com.
FAU - Gong, Jason
AU  - Gong J
AD  - Pfizer Inc., Global Product Development, New York, NY, USA.
FAU - Canas, George C
AU  - Canas GC
AD  - Prism Research Inc., Prism Clinical Research, St. Paul, MN, USA.
FAU - Winkle, Peter
AU  - Winkle P
AD  - Anaheim Clinical Trials, Orange, CA, USA.
FAU - Pelletier, Kathleen
AU  - Pelletier K
AD  - Pfizer Inc., Global Product Development, Groton, CT, USA.
FAU - LaBadie, Robert R
AU  - LaBadie RR
AD  - Pfizer Inc., Global Product Development, Groton, CT, USA.
FAU - Ginman, Katherine
AU  - Ginman K
AD  - Pfizer Inc., Global Product Development, Groton, CT, USA.
FAU - Pithavala, Yazdi K
AU  - Pithavala YK
AD  - Pfizer Inc., Global Product Development, San Diego, CA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03542305
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20220111
PL  - France
TA  - Eur J Drug Metab Pharmacokinet
JT  - European journal of drug metabolism and pharmacokinetics
JID - 7608491
RN  - 0 (Aminopyridines)
RN  - 0 (Lactams)
RN  - 0 (Pyrazoles)
RN  - OSP71S83EU (lorlatinib)
SB  - IM
EIN - Eur J Drug Metab Pharmacokinet. 2022 Mar 8;:. PMID: 35258796
MH  - Adult
MH  - *Aminopyridines/adverse effects/pharmacokinetics
MH  - Area Under Curve
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Humans
MH  - *Lactams/adverse effects/pharmacokinetics
MH  - Lung Neoplasms/drug therapy
MH  - *Pyrazoles/adverse effects/pharmacokinetics
MH  - *Renal Insufficiency/drug therapy
PMC - PMC8917008
COIS- SL was an employee of Pfizer Inc. at the time of the study; JG is an employee of 
      Pfizer Inc.; GCC and PW have no conflicts of interest; KP, RRL, KG, and YKP are 
      employees of Pfizer Inc. and own stock in Pfizer.
EDAT- 2022/01/13 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/01/11
CRDT- 2022/01/12 06:42
PHST- 2021/12/12 00:00 [accepted]
PHST- 2022/01/13 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2022/01/12 06:42 [entrez]
PHST- 2022/01/11 00:00 [pmc-release]
AID - 10.1007/s13318-021-00747-4 [pii]
AID - 747 [pii]
AID - 10.1007/s13318-021-00747-4 [doi]
PST - ppublish
SO  - Eur J Drug Metab Pharmacokinet. 2022 Mar;47(2):235-245. doi: 
      10.1007/s13318-021-00747-4. Epub 2022 Jan 11.