FARMAKOKINETIKA & FARMAKODINAMIKA

PADA ZERO GRAVITASI

 PHYSIOLOGICAL CHANGES IN SPACE

FASE RESPON AWAL(3 - 6 MINGGU):

-PERUBAHAN RESEPTOR NEUROVESTIBULAR

-FUNGSI SYMPATHETIC AND PARASYMPATHETIC

-VOLUME CAIRAN

-METABOLISM

-HEMODYNAMICS AND ENDOCRINE REGULATION

-DISTRIBUSI CAIRAN("BIRD LEGS" AND "PUFFY FACE“)

FASE ADAPTASI(BEBERAPA BULAN):

-MASSA TULANG BERKURANG

-PERUBAHAN FUNGSI NEUROTRANSMITTER & RECEPTOR

-PENURUNAN RESPONDS IMUN

-PENURUNAN FUNGSI SSP

 PHARMACOKINETICS IN SPACE
ABSORPTION AND BIOAVAILABILITY

-RUTE PER ORAL LEBIH DISUKAI DALAM MINUM OBAT

-ADA PERBEDAAN PREFLIGHT AND IN-FLIGHT SALIVARY LEVELS OF

ACETAMINOPHEN DIKARENAKAN WAKTU TRANSIT OBAT DI GIT

-ADA PERBEDAAN SALIVARY LEVELS TABLET ORAL SCOPOLAMINE

ANTARA PREFLIGHT DAN IN FLIGHT.
 PHARMACOKINETICS IN SPACE
ABSORPTION AND BIOAVAILABILITY

FAKTOR YANG MEMPENGARUHI ABSORPSI:

-KECEPATAN PENGOSONGAN LAMBUNG DIPENGARUHI OLEH VOLUME,

CALORIES, EXERCISE, SIZE AND DENSITY OF PARTICLES, TEMPERATURE,
VISCOSITY AND OSMOLALITY, AND FACTORS ASSOCIATED WITH
PHYSIOLOGIC RESPONSES (BODY POSITION AND ELECTROLYTE
BALANCE)

-PERUBAHAN UKURAN PARTIKEL OLEH LAMBUNG

-PERGERAKAN PARTIKEL KE SELURUH LAMBUNG(VARIABILITY ANTAR

INDIVIDU)

-EFEK MOTION SICKNESS

-MASSA
 DISTRIBUTION
VOLUME OF DISTRIBUTION. PHYSIOLOGICAL CHANGES LIKE THE
DECREASE IN TOTAL BODY WATER AND PLASMA VOLUME, TISSUE
PERFUSION, AND MUSCLE MASS LOSS MAY ALTER THE VOLUME
OF DISTRIBUTION OF DRUGS. THIS MAY HAVE AN IMPACT ON THE
PLASMA AND TISSUE CONCENTRATIONS ACHIEVED AFTER
ADMINISTERING A DRUG IN SPACE, AND DEPENDING ON THE
MAGNITUDE OF THE CHANGE, MAY REQUIRE A COMPLETELY
NEW DOSING SCHEME TO BE DESIGNED TO AVOID
SUBTHERAPEUTIC OR TOXIC CONCENTRATIONS.
 DISTRIBUTION
BINDING. DRUG BINDING IN BLOOD OCCURS TO DIFFERENT
STRUCTURES AS PLASMA PROTEINS, LIPIDS AND ERYTHROCYTES.
AS ONLY THE UNBOUND FRACTION OF DRUG IS ACTIVE,
CHANGES IN TOTAL PLASMA PROTEINS WILL AFFECT
PHARMACOKINETICS. DURING SPACE FLIGHT NO SIGNIFICANT
CHANGES IN PLASMA PROTEIN CONCENTRATIONS HAVE BEEN
OBSERVED, BUT A REDUCTION IN RED BLOOD CELL MASS
(HEMOGLOBIN AND NUMBER OF ERYTHROCYTES) IS REPORTED.
ALTERED TISSUE BINDING IS OBSERVED AS A RESULT OF PROTEIN
LOSS, MUSCLE ATROPHY AND DECREASE IN LEAN BODY MASS.
 ELIMINATION - CLEARANCE AND METABOLISM

-CLEARANCE IS DEFINED AS THE VOLUME OF BODY FLUID CLEARED PER TIME UNIT,
CAN BE EXPRESSED AS THE PRODUCT OF BLOOD FLOW ACROSS AN ELIMINATING
ORGAN AND THE RESPECTIVE EXTRACTION RATIO

-BECAUSE PLASMA VOLUME IS DECREASED DURING SPACE FLIGHT THERE MIGHT BE A

POSSIBILITY OF CHANGES IN ORGAN PERFUSION.

-STUDIES IN ANTI-ORTHOSTATIC BED REST DID NOT SHOW A SIGNIFICANT CHANGE IN

HEPATIC BLOOD FLOW OR EFFECTIVE RENAL PLASMA FLOW.

-AMOUNTS OF CYTOCHROME P-450 ISOFORMS AND OTHER ENZYMES WERE SHOWN

TO DECREASE DURING SPACE FLIGHT AND SIMULATED UG, SUGGESTING THAT
XENOBIOTIC METABOLISM MAY ALSO BE ALTERED BY SPACE FLIGHT.

-ALTHOUGH GENERALIZED PREDICTIONS OF THE EFFECT OF UG ON DRUG

METABOLISM CANNOT BE MADE BASED ON THESE OBSERVATIONS, THESE
ALTERATIONS COULD RESULT IN HIGHER PLASMA LEVELS OF SOME DRUGS,
ESPECIALLY LOW-EXTRACTION DRUGS, AND INCREASED INCIDENCE OF ADVERSE
EFFECTS.
 PHARMACODYNAMICS IN SPACE

-Little is known about the effect of uG on pharmacodynamics.

Pharmacodynamic changes due to microgravity are hard to
evaluate since the dose-response relation is a hybrid: it depends
on pharmacokinetic characteristics, pharmacodynamic
characteristics or both. In addition, post-receptor events that
cause the ultimate expression of a ligand-recognition site
interaction as clinically apparent effects remain to be fully
elucidated. Conversely, the pharmacological changes that
may be observed during space flights are more likely to be
resulting from the physiological perturbations that arise from
exposure to uG. Intra and inter-individual variability in
pharmacological response to medications can also be caused
by factors such as stress, lack of sleep, and change in
chronophysiologic status. All these factors have been reported
to affect astronauts during space flights. These changes
however, are expected to be quantitative and not qualitative.
For example, in a retrospective study, Bagian et al46 observed a
much lower incidence of sedation than expected with
intramuscular promethazine during space flights.
TERIMA KASIH