PMID- 29982257
OWN - NLM
STAT- MEDLINE
DCOM- 20181127
LR  - 20181127
IS  - 1423-0313 (Electronic)
IS  - 0031-7012 (Linking)
VI  - 102
IP  - 3-4
DP  - 2018
TI  - Quantification of Hydrochlorothiazide and Ramipril/Ramiprilate in Blood Serum and 
      Cerebrospinal Fluid: A Pharmacokinetic Assessment of Central Nervous System 
      Adverse Effects.
PG  - 133-137
LID - 10.1159/000489999 [doi]
AB  - BACKGROUND: A drug must reach the central nervous system (CNS) in order to 
      directly cause CNS adverse effects (AEs). Our current study addressed the 
      pharmacokinetic (PK) background of the assumption that CNS concentrations of 
      hydrochlorothiazide (HCT) and ramiprilate may directly cause CNS AEs such as 
      headache and drowsiness. METHODS: In neurological patients, paired serum and 
      cerebrospinal fluid (CSF) samples were withdrawn simultaneously. Some of them 
      were treated with HCT (n = 15, daily chronic doses 7.5-25 mg) or ramipril (n = 9, 
      2.5-10 mg). Total concentrations of HCT and ramiprilate were quantified in these 
      samples. To this end, sensitive liquid chromatography/tandem mass spectrometry 
      methods were developed. RESULTS: CSF reached 4.1% (interquartile ranges 2.5-5%) 
      of total serum concentrations for HCT and 2.3% (1.7-5.7%) for ramiprilate, 
      corresponding to about 11.3% and 5.5% of respective unbound serum concentrations. 
      CONCLUSION: The PK/Pharmacodynamic characteristics of HCT and ramiprilate in the 
      CNS are unknown. However, since the CSF levels of these agents, both free and 
      bound, were much lower than the corresponding concentrations in serum, it is 
      unlikely that the observed CNS AEs are mediated primarily via direct effects in 
      the brain.
CI  - (c) 2018 S. Karger AG, Basel.
FAU - Sigaroudi, Ali
AU  - Sigaroudi A
AD  - Department I of Pharmacology, University Hospital Cologne, Cologne, Germany.
AD  - Department of Clinical Pharmacology and Toxicology, Zurich University Hospital, 
      Zurich, Switzerland.
FAU - Kinzig, Martina
AU  - Kinzig M
AD  - Institute for Biomedical and Pharmaceutical Research, Nuremberg, Germany.
FAU - Wahl, Oliver
AU  - Wahl O
AD  - Institute for Biomedical and Pharmaceutical Research, Nuremberg, Germany.
FAU - Stelzer, Christoph
AU  - Stelzer C
AD  - Institute for Biomedical and Pharmaceutical Research, Nuremberg, Germany.
FAU - Schroeter, Michael
AU  - Schroeter M
AD  - Department of Neurology, University Hospital Cologne, Cologne, Germany.
FAU - Fuhr, Uwe
AU  - Fuhr U
AD  - Department I of Pharmacology, University Hospital Cologne, Cologne, Germany.
FAU - Holzgrabe, Ulrike
AU  - Holzgrabe U
AD  - Institute of Pharmacy and Food Chemistry, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Sorgel, Fritz
AU  - Sorgel F
AD  - Institute for Biomedical and Pharmaceutical Research, Nuremberg, Germany.
AD  - Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20180706
PL  - Switzerland
TA  - Pharmacology
JT  - Pharmacology
JID - 0152016
RN  - 0 (Antihypertensive Agents)
RN  - 0J48LPH2TH (Hydrochlorothiazide)
RN  - L35JN3I7SJ (Ramipril)
SB  - IM
MH  - Aged
MH  - Antihypertensive Agents/adverse effects/*blood/*cerebrospinal 
      fluid/pharmacokinetics
MH  - Blood-Brain Barrier/metabolism
MH  - Female
MH  - Humans
MH  - Hydrochlorothiazide/adverse effects/*blood/*cerebrospinal fluid/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Ramipril/adverse effects/*blood/*cerebrospinal fluid/pharmacokinetics
OTO - NOTNLM
OT  - Blood arachnoid barrier
OT  - Blood brain barrier
OT  - Blood central nervous system barrier
OT  - Blood cerebrospinal fluid barrier
OT  - Central nervous system adverse effects
OT  - Central nervous system side effects
OT  - Neuropharmacokinetics
EDAT- 2018/07/10 06:00
MHDA- 2018/11/28 06:00
CRDT- 2018/07/09 06:00
PHST- 2018/05/04 00:00 [received]
PHST- 2018/05/09 00:00 [accepted]
PHST- 2018/07/10 06:00 [pubmed]
PHST- 2018/11/28 06:00 [medline]
PHST- 2018/07/09 06:00 [entrez]
AID - 000489999 [pii]
AID - 10.1159/000489999 [doi]
PST - ppublish
SO  - Pharmacology. 2018;102(3-4):133-137. doi: 10.1159/000489999. Epub 2018 Jul 6.