Ampicillin and Amoxicillin Pharmacokinetics

Absorption

A) Bioavailability
1) Oral, fasting state: 50%
a) No significant bioavailability differences between products has been
reported .

2) Diarrhea has variable effect on absorption .

3) Absorption from peritoneal cavity produces serum concentrations in renal

failure patients comparable to an IM dose in healthy individuals .

B) Effects of Food

1) Food delays or reduces oral absorption.

Distribution sites

a) Protein Binding 20%

b)Tissues and Fluids

1) Bronchial secretions: 3.2% to 5.2% of peak blood concentration

2) Bile: 0.4 to 6.5 mcg/mL

a) Biliary concentrations of 0.4 to 6.5 mcg/mL in a 12-hour period occurred

after oral ampicillin 0.5g

b) Therapeutic concentrations of ampicillin are not obtained with obstructive

biliary tract disease. In patients with a patent tract or cholelithiasis without
obstruction of the common bile duct or cystic duct, bile levels of ampicillin
average 22.3 mcg/mL 2 hours after dose in the common duct. In the
presence of cholelithiasis, ampicillin levels are 13.1 mcg/mL 2 hours after the
dose to 36 mcg/mL 4 hours after dose.

3) Cerebrospinal fluid: only with inflamed meninges.

a) Cerebrospinal fluid and brain penetration occurs only with inflamed

meninges.
4) Kidney: 50% to 80% of serum concentrations.

a) Cortical and papillary renal concentrations are about 50% of

corresponding serum levels, and 80% of serum values in the outer medulla in
diseased kidneys. Hydropenic states decrease the ability of ampicillin to
collect in renal tissue by 7 times, compared to normal kidney function.

5) Placenta: crosses

a) Ampicillin is detectable in amniotic fluid, cord serum, and in the infant.

Therapeutic concentrations have been reported, but data are not conclusive

8) Sputum: 1.4 mg/L

a) Peak concentrations of 1.4 mg/L of ampicillin in sputum occurred after

intravenous bolus doses of 500 mg in 5 patients with chronic bronchitis

Distribution Kinetics
1)Ampicillin volume of distribution.

19.5 to 27 L
In 9 patients with cirrhosis, the Vd was increased .
Vd in newborns is approximately 0.82 L/kg .
Vd in pregnancy is approximately 177 mL/kg .

2) Ampicillin Sodium

a) Volume of Distribution
19.5 to 27 L

b) In 9 patients with cirrhosis, the Vd was increased

c) Vd in newborns is approximately 0.82 L/kg
d) Vd in pregnancy is approximately 177 mL/kg

Excretion
Kidney

Ampicillin
Renal Clearance (rate)
280 mL/min
Renal Excretion (%)
34% to 64%
Following oral administration; approximately 40% is excreted
unchanged in the urine .
 About 34% to 64% of a single oral dose is eliminated in the urine
during the 6 or 8 hours, respectively, after administration.

Ampicillin Sodium
Renal Clearance (rate)
-280 mL/min
Renal Excretion (%)
-79% to 92%, following a parental dose , 79-92% remain unchanged.

Bile

1) Ampicillin
Concurrent probenecid administration can increase biliary excretion
to about 0.2%
2) Ampicillin Sodium
Ampicillin is excreted in bile, concentrations of the active form are
higher in bile than those in the serum
Concurrent probenecid administration can increase biliary excretion
to about 0.2%

Elimination Half life

A) Parent compound
Ampicillin and Ampicillin Sodium- 1 to 1.9 hrs (normal patients ), 4 to
5 hrs in renal failure , 15 to 20 hours in oliguria, 2 to 4 hrs in new
born , up to 6hrs in premature infant, and 1.6 hours in pregnancy

Amoxicillin- Pharmacokinetics

Absorption-
T max, oral: 1 to 2 hours ( immediate release ) , 3.1 hours extended
release
Bioavailability, amoxicillin absorption may be greater and less
variable with ampicillin.
Absorption is dose dependent at doses greater than 1000mg,
approximately 2g of amoxicillin is the maximum amount that can be
absorbed after a single dose.
As the dose of amoxicillin increases the percent of drug absorbed
decreases.
Effects of food- Immediate- release: no effect when administered at the start
of a light meal
Extended- release: rate of absorption is decreased, extent
is not affected
Amoxicillin is stable in the presence of gastric acid, however the effect
of food on absorption has only been studies when amoxicillin 400 and
875mg formulations were administered at the start of the light meal
Ingestion of amoxicillin with food produces levels within the
therapeutic range
Administration of extended release amoxicillin with food resulted in a
decreased rate of absorption as evidenced by a lower Cmax and longer
Tmax compared with immediate release of oral suspension, but the
extent of absorption was similar as evidenced by comparable AUCs.

Distribution- protein binding: approximately 20%

Protein binding 20%

Tissue and fluids
Bile : exceeds minimum inhibitory concentration (MIC) for most
bacteria
Following 1 g IM dose of amoxicillin, levels measured in the bile
exceed the MIC values for most of the bacteria usually
considered
After doses of amoxicillin 3g/day mean bile concentrations were
19 mcg/ml. Concomitant administration of probenecid resulted in
higher biliary concentrations of amoxicillin.
Cerebrospinal fluid: Occurs with inflamed meninges: distribution
into the brain and spinal fluid occurs when the meninges are
inflamed. After a 100-mg oral dose of amoxicillin, cerebrospinal
fluid concentrations reached 0.1 to 1.5 mcg/ml, after 2-g dose ,
CSF concentration varied from 40 mcg/ml at 1.5 hours to 27
mcg/ml at 4 hours.
Interstitial After 1 g IM dose - levels wee
therapeutic
Liver Exceeds MIC level
Lungs Exceeds MIC level
 Middle ear fluid Exceeds MIC level ( doses 25
mg/kg)
Pleural fluid Exceeds MIC level of common
gram positive bacteria ( dose
750 mg)

Excretion- Renal -60%

Elimination half-life Immediate-release, 61.3 minutes , extended
release, 1.5hours, extended release amoxicillin did not accumulate
with once daily dosing of 775mg for 7 days
A half-life of 2 hours to 15 hours is reported in 5 patients with renal
failure who received 750mg/day orally, in patients with renal failure the
half-life ranges from 5 to 20
hours.

Extracorporeal elimination

Hemodialysis- dialyzable
Amoxicillin can be removed from circulation by hemodialysis
Dialysis reduces amoxicillin half-life to 2.2 to 4.5 hours