Effects Of Hyperbaric Exposure on Drug Disposition
A few studies have examined the disposition of drugs and drug
effects at increased environmental pressure. Studies in awake dogs at pressures
up to 6 ATA and ambient PO2
up to 2.8
ATA have shown that liver plasma flow decreases when either ambient pressure or PO2
is raised. There was an apparent increase in plasma volume at 1.3 ATA and a return
toward 1 ATA values at higher pressures.
TABLE 70-5 -- Mean blood acid-base and cardiovascular responses to altitude exposure and
hyperbaric oxygenation in 14 normal subjects
|
|
Arterial Blood |
Mixed Venous Blood |
|
|
|
|
|
|
|
Atmospheric Pressure (ATA) |
Inspired Gas |
PO2
(mm Hg) |
pH |
PCO2
(mm Hg) |
O2
Saturation (%) |
PO2
(mm Hg) |
pH |
PCO2
(mm Hg) |
O2
Saturation (%) |
Cardic Output (L·min-1
) |
Mean Arterial Pressure (mm
Hg) |
Mean Pulmonary Artery Pressure
(mm Hg) |
PA Wedge Pressure (mm Hg) |
Systemic Vascular Resistance
(dyne·sec·cm-5
) |
Pulmonary Vascular Resistance
(dyne·sec·cm-5
) |
|
0.56 (4572-m altitude) |
Air |
38 |
7.46 |
32 |
73.4 |
30 |
7.44 |
36 |
57.1 |
9.1 |
87 |
18 |
10 |
762 |
83 |
|
1 |
Air |
94 |
7.40 |
37 |
95.7 |
43 |
7.39 |
42 |
75.5 |
6.5 |
86 |
13 |
9 |
1061 |
64 |
|
3 |
100% O2
|
1542 |
7.42 |
36 |
99.1 |
399 |
7.37 |
43 |
97.7 |
5.8 |
95 |
12 |
9 |
1286 |
41 |
|
Data from McMahon TJ, Moon RE, Luschinger BP, et
al: Nitric oxide in the human respiratory cycle. Nat Med 8:711, 2002. |
In the same studies, plasma volume was inconsistently affected by ambient pressure,
but reduced by increases in PO2
.[85]
Major pharmacokinetic or pharmacodynamic differences would not
be expected for most drugs up to the pressures used for most clinical purposes (up
to 6 ATA). Indeed, up to 6 ATA the pharmacokinetics of meperidine[86]
and pentobarbital[87]
is unchanged under hyperbaric
and hyperoxic conditions in the dog. Canine studies have also demonstrated no alteration
in either theophylline[88]
or salicylate[89]
kinetics at ambient pressures up to 6 ATA and inspired PO2
up to 2.8 ATA.
Stoudemire and associates[90]
described the use of benzodiazepines, chlorpromazine, and lithium carbonate for the
treatment of agitation, auditory and visual illusions, and paranoia in a previously
normal subject participating in an experimental dive to 650 m (66 ATA). The symptoms,
poorly controlled with diazepam, 120 mg, and temazepam, 60 mg/day, ultimately responded
to chlorpromazine, 300 mg/day. Lithium carbonate subsequently administered in conventional
doses appeared to display normal pharmacokinetics. Although the effect of chlorpromazine
appeared to be appropriate clinically, the authors were uncertain whether the failure
of benzodiazepines to elicit a desired therapeutic response was due to the patient's
condition or a pressure reversal phenomenon.
In summary, clinical experience and the published literature indicate
that for a variety of drugs, conventional parenteral drug dosing schedules may be
used safely under hyperbaric conditions at the pressures used for the clinical treatment
of patients with HBO therapy.
