Back to the Top
There seems to have a lot of discussion in this group about research
issues. I would like to encourage those of us who works in the clinical
field of pharmacokinetics to write too.
To start the discussion, here is a patient case: a women (73 y) is treated
with gentamycine and vancomycine for endocarditis. Blood levels for both
drug has been taken the same day.
After calculation, the Vd for gentamycine was 0.15 L/Kg (mean in our
hospital is 0.32 L/Kg) and the Vd for Vancomycine was 0.68 L/Kg (mean in
our hospital is 0.76 L/Kg). Does anyone has explainations for such
discrepancy between the very low Vd of Gentamycine and the relatively
normal Vd of Vancomycine ?
Thanks...
-Is your Vd(gent) based on lean body mass or actual body weight?Back to the Top
Aminoglycoside disposition should be base on LBW,DW(=ABW-IBW *40% + IBW), or
ABW using the most appropriate value for the given patient.
- Maybe phlebotimist obtained the draw from an IV access line say that has
just been flushed with saline (i.e. error in sample acquisiton) instead of
"straight stick".
- Geriatric patients, espically female(s) have proportionatly higher
composition of adipose mass than younger (<65yo) patients, so volumes of
distributions will/should be in lower quartile of range.
I would be glad to provide you with references to subsantiate any of the
these statements upon request.
Back to the Top
Vancomycin has a higher degree of protein binding than gentamicin. As a
result vancomycin volume of distribution may vary with due to variability in
protein binding. This is independent of changes in extracellular water
status in the patient which may alter volume of distribution of both drugs.
Back to the Top
Would you be able to provide us with some other kinetic information, such
as height, weight, nutritional status, etc.? Thanks.
Marc Semprebon, RPh, MSLS
DHMC
Lebanon, NH 03756
Back to the Top
Michael,
Could you expand the baseline database? Condition on admission, PMH,
both drugs at steady state, pert. lab values.
Back to the Top
Population parameters based on one compartment models partially on the
time of the serum concentration draw post the end of the infusion. Since
outliers can exist, some patients may have aminoglycoside Vd values on the
low side. The earlier the "peak" draw will also tend to give lower Vd
values. We also can't forget about the assumption that the patient
recieved the correct dose. If a error occured here, we may never know.
Generally, I question any value less then 0.2 L/kg adjusted weight, and if
terapy is long term (as in Endocarditis), I might repeat the level if
their is a clinical reason to adjust the dose.
For more info on Aminoglycoside Vd's and different populations:
Dager We. Aminoglycoside Pharmacokinetics: Volume of distribution in
specific adult patient subgroups. Ann Pharmacother 1994;28:944-51
Vancomycin: The population range is 0.5-1.1 l/kg, and also depends on how
long you wait to draw the level.
William Dager, Pharm.D.,FCSHP
Cordinator, Pharmacokinetics Consult Service
University of California, Davis Medical Center
Back to the Top
To those of you who request more information from the case I have sumitted
last week,
here is the details:
------------------
----------Sex: Male
Age: 74 y
Real weight: 73.4 Kg
Height: 1.72 m
------------------
----------Diagnosis on admission: Previous Diagnosis:
Cerebral Stroke Chronic Atrial Fibribrillation
Endocarditis (MRSA) Pulmonary neoplasm
(resection in 05/96)
MPOC
NIDDM
------------------
----------Rx List on day 2:
Gentamycin 100 mg q12h (at 7:00 and 19:00)
Vancomycin 750 mg q12h (at 5:00 and 17:00)
NaCl 0.45% 30 ml/h (for IV administration of ATB)
Rifampicin 600 mg bid
Salbutamol/Ipratropium/Beclomethasone 2 inh qid
Digoxine 0.125 mg die
Diltiazem CD 180 mg die
Nitrospray prn
Oxazepam 30 mg hs
Furosemide 20 mg die
KCl 20 mEq die
Glyburide 5 mg die
Warfarine
------------------
----------Lab: Serum Creatinine: 95 mmol/L (on day 2)
No fever
Arterial tension: normal
Glycemia: normal
------------------
----------Serum sample were that on the third dose of genta and vanco. The
results:
Genta: Cp: 0.44 mg/L 10 min before next dose
3.55 mg/L 170 min after end of the infusion
(administred in 60 min)
2.17 mg/L 370 min after end of the infusion
Calculated value:
Dosing weight: 67.75 Kg
CpMax: 6.56 mg/L
CpMin: 0.44 mg/L
Total Vd: 11.42 L
Vd/RW: 0.15 L/Kg
Vd/DW: 0.17 L/Kg
Half-life: 2.82 hr
ClRx: 0.79 ml/sec
------------------
----------Vanco: Cp: 7.56 mg/L 10 min before next
dose
19.4 mg/L 60 min after end of infusion
(administred in 60 min)
Calculated value:
CpMax: 21.32 mg/L
CpMin: 7.56 mg/L
Total Vd: 49.58 L
Vd/RW: 0.68 L/Kg
Vd/DW: 0.73 L/Kg
Half-life: 7.35 hr
ClRx: 1.30 ml/sec
------------------
----------Dosing was repeated after 6 days, Vanco result was similar, but
Genta results return
to nomal (Vd: 0.31 L/Kg).
------------------
----------Any explaination for the low Vd of Genta?
Marc-Andre Paradis, pharm.
Back to the Top
In review of the presented pharmacokinetic information on this 74 yo male
on gentamicin and vancomycin, I calculate the following:
*a volume of distribution of 0.28L/kg on his ABW and 0.31L/kg on the original
set of levels, using the PEAK and RANDOM levels to calculate out kel, which
were:
* kel of 0.15/hr with a t 1/2 of 4.6 hrs.
This data would be more representative of a patient with a q12h dosing
interval.
If, however, one uses only the trough and peak (0.44mg/L and 3.55 mg/L),
one arrives at a kel and t 1/2 of 0.28/hr and 2.5 hrs, respectively. The Vd
calculated from this is therefore 11.7 liters.
Given the age of the patient, I would believe the data that best fits the
age and renal function of the patient. Calculating out the parameters from
different levels (as I did) confirms the repeat set of levels. I would have
evaluated the first set and would have recommended to NOT repeat levels. In
review, the original information was misleading, and there was a
pharmacokinetic/mathematical reason for the low Vd.
Marc Semprebon, RPh, MSLS
Clinical Pharmacist
Department of Pharmacy Services
Dartmouth-Hitchcock Medical Center
One Medical Center Drive
Lebanon, NH 03756
(603) 650-5000 pager #9827
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)