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The following message was posted to: PharmPK
Dear Colleagues
This laboratory analyses postmortem blood samples from deceased individuals
as part of the Coronial Inquest. We have had a number of post-operative
deaths and metoclopramide was identified in the blood (not surprising).
What is the expected range of concentrations for i.v. metoclopramide in a
hospital environment as compared with patients taking the drug orally at
home?
thanks in advance
Dr Kathryn Campbell
Forensic Science Service Tasmania
20 St Johns Avenue
NEW TOWN 7008
ph: 03 6278 5625
fax: 03 6278 5693
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The following message was posted to: PharmPK
Dear Kathryn,
Would data from parenteral formulations of metoclopramide given to
19 healthy male volunteers help ? We gave the standard
hydrochloride monohydrate iv as a reference and a pH neutral form
iv and i'm to test the hypothesis that the neutral form would be
better tolerated.(Rotmensch HH et al, 1997, J Clin Pharmacol
37:222-228). The dose as 1.8 mg/kg. The basic Pk parameters
were: AUC(mcg/ml/hr) 4.06+/-1.81, Cmax(ng/ml) 916.2+/-60.1,
tmax (hr) 0.66 +/- 0.79,t1/2(hr) 5.18+/-1.46, Cl(L/hr/kg) 0.48+/-
0.16, Vd(L/kg) 3.29+/-0.8. Our volunters were probably heavier than
your patients and the subjects who completed our study had a
mean weight of 75.4 kg (range 63.0 - 96.5 ). Do give us a call if you
need any further details.
Andrew Sutton.
Guildford Clinical Pharmacology
q.-at-.gcpl.co.uk
+44 (0) 1483 406886
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The following message was posted to: PharmPK
Dr. Campbell,
The mean Cmax in healthy volunteers following a 20mg oral dose is
80ng/ml. The time to Cmax (Tmax) is one to two hours, the fraction
orally absorbed is 80 +/- 15 percent,the average Vd is 3.5 L/Kg, and
the average half-life with normal renal function is 5-6 hours
(Ke = .126hr-1). With an average oral dose of 10-20mg TID, the
expected average steady-state levels from a 20mg TID Dose would be in
the area of :
Cssave= FSD/CLTau
Cssave= (0.8)(1)(20mg)/(.126)(3.5L/kg x 70Kg)(8 hours)
= .0647 mg/L= 64.7 ug/L= 64.7 ng/ml
The average steady state dose for IV dosing of 20mg TID would be
in the area of:
Cssave= SD/CLTau=
Cssave= (1)(20mg)/(.126)(3.5L/Kg x 70Kg)(8 hours)
= .081mg/L= 81.0ug/L= 81.0ng/ml.
Thinking in terms of peak/trough concentrations, the peak
concentration in an oral 20mg TID regimen in a 70Kg patients would be
in the area of;
Cpeak1stdose= FSD(e-Ketmax)/Vd
= (0.80(1)(20mg)(e-.126(1.5))/(3.5x70)
= .054mg/L= 54ug/L= 54ng/ml
Ctrough1stdose= Cpeak(e-ke(Tau-Tmax))
= 54ng/ml(e-.126(6.5)=
= 23.8ng/ml
Cpeakss= [FSD(e-Ketmax)]/[Vd(1-e-keTau)]
= (.8)(1)(20mg)(e-.126(1.5))/[(3.5x70)(1-e-.126(8))]
= .102mg/L= 102ug/L= 102ng/ml
Ctroughss= Cpeak(e-Ke(Tau-tmax))=
= (102ng/ml)(e-.126(6.5))
= 45.0ng/ml
Applying the same treatment to IV bolus dosing in a 70Kg patient,
the peak/tough concentrations in a 20mg IV TID regimen would be in
the area of;
Cpeak1stdose= Xo/Vd
= 20mg/(3.5x70)
= 81.6 ug/L= 81.6ng/ml
Ctrough1stdose= Cpeak(e-Ke(Tau))
= (81.6ng/ml)(e-(.126(8))
=29.8ng/ml
Cpeakss= [Xo/Vd]/[1-e-KeTau]
= (20mg/(3.5x70)/[1-e-.126(8)]
= 128.5ng/ml
Ctroughss= Cpeakss(e-KeTau)
= 128.5ng/ml(e-.126(8))
= 46.9ng/ml
The above figures could be modified to patients of different
weights by modifying the Vd in the equations. The Ke could also be
modified according to renal function.
However, much higher doses of metoclopramide are used in
hospitalized chemotherapy patients to counteract drug-induced nausea.
In these cases, the resulting serum concentrations could be much
higher depending on when the last metoclopramide dose was given. In
addition, serum levels could also be higher in patients with a
history of renal failure.
Mike Leibold, PharmD, RPH
ML11439.at.goodnet.com
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