pharmacokinetics ampicillinceftriaxonevancomycin half-life: 1-1.8 hr protein bound: 15-25%...

PharmacokineticsAmpicillin Ceftriaxone Vancomycin

Half-Life:

1-1.8 hrProtein Bound: 15-25%Absorption: oral 50%Metabolism: hepaticExcretion: urine

Half-Life:

5-9 hrProtein Bound: 85% to 95%Absorption: IM: well absorbedMetabolism: liverExcretion: urine (33%-65%); feces

Half-life:

5-11 hrDistributionwidely in body tissues and fluidProtein Bound: 10-50%Excretion (IV): urine (oral): feces

PharmacokineticsRifampin Meropenem

Absorption: oral well absorbed

Distribution: highly lipophilic; crosses blood-brain barrier well Protein Bound: 80%Half-life 3-4 hrMetabolism: hepatic; undergoes enterohepatic recirculationExcretion: feces (60-65%) and urine (~30%) as unchanged drug

Vd: adults: ~0.3 L/kgDistribution: penetrates

well into most body fluids & tissues; Protein Bound: 2%Metabolism: hepatic Excretion: urine (~25% as inactive metabolites)Half-Life 1-1.5 hr

Pharmacotherapy of meningitisBecause herpes encephalitis can resemble bacterial meningitis at

presentation

acyclovir is usually included with the initial empirical therapy, IV 10-15 mg/kg/dose every 8 hours for 10-14-21 days

Pharmacokinetics• Absorption: oral: 15-30%• Protein Bound: 9-33%• Half-life: 3 hr• Peak Plasma TimeOral: within 1.5-2 hrIV: within 1 hr• Metabolism: hepatic (small amounts)• Excretion: urine (30-90% as unchanged drug)

Pharmacokinetics of dexametasone

• Half-Life: 2-3.5 hr

• Onset: IM: 8-24 hrPeak Plasma Time:

IM: within 8 hr PO: 1-2 hr

• Vd: 2 L/kg• Metabolism: liver• Excretion: mainly in urine,

minimally in bile

Levodopa The main pharmacokinetics parametres

• Peak Plasma Time: 0.5 hr (conventional), 2 hr (XR);• Peak Plasma Concentration: XR is 35% conventional. • Duration 5 hr (short duration improvement), 3-5

days (long duration response). • Vd: levodopa 65% body weight• Protein Bound: 10-30%• Metabolism: hepatic metabolism• Excretion: Urine (80-85%)

Dopamine agonists • Apomorphine. Initial: 2 mg (0.2 mL) SC The main pharmacokinetics parametres • Peak Plasma Time:10-60 min. • Half-life, elimination: 30-60 min.• Vd: 218 L. • Metabolism: hepatic metabolism. • Excretion: Urine (93%); feces (16%).

Dopamine agonists• Pramipexole The main pharmacokinetics parametres• Peak Plasma Time: 2 hr (IR); 6 hr (ER), • Bioavailability: >90%. • Protein Bound: 15%/• Vd: 500 L. • Metabolism <10%. • Half-Life: 8 hr (12 hr in elderly)/• Excretion: urine 90%.

Dopamine agonists

• Ropinirole The main pharmacokinetics parametres• Peak Plasma Time: (Conventional) 1-2 hr; (ER) 6-10

hr. • Bioavailability: 55%.• Protein Bound: 40%. • Half Life: (ER): 6 hr.• Vd: 525L. • Metabolism: Hepatic CYP1A2. • Excretion: Urine.

Dopamine agonists• Rotigotine The main pharmacokinetics parametres• Bioavailability: 37%. • Peak plasma time: 15-18 hr. • Protein Bound: 92% (in vitro); 89.5% (in vivo).• Vd: 84 L/kg. • Metabolism: hepatic. • Half-life, biphasic: 3 hr (initial); 5-7 hr (terminal). • Excretion: 71% urine; 23% feces.

Antiviral drug • Amantadine The usual dosage is 100 mg given twice a day when

used alone. The main pharmacokinetics parametres • Onset: Within 48 hr (antidyskinetic). • Peak plasma time: 2-4 hr. • Half-life elimination: 16 hr (avg; normal renal

function).• Vd: 3-8 L/kg. • Protein Bound: 67%. • Bioavailability: 86-90%. • Metabolism: hepatic• Excretion: Urine (80-90% unchanged)

Anticholinergics• Trihexyphenidyl • Initial: 1 mg PO first day, then increase by 2 mg q3-

5days until reach 6-10 mg/days.• Maintenance: 5-15 mg/day PO divided q6-8hr. The main pharmacokinetics parametres• Half-Life elimination: 33 hr. • Onset: 1 hr. • Peak effects: 1.3 hr. • Duration: 6-12 hr. • Metabolism: Unknown. • Excretion: Urine and bile.

Anticholinergics• Benztropine mesylate 1-2 mg/day (range 0.5-6 mg)

PO/IV/IM qHS OR divided q6-12hr. • Initiate at low doses (0.5-1 mg) qHS and titrate by 0.5

mg q5-6Days.The main pharmacokinetics parameters • Onset of action: 1hr (PO); 15 min (parenteral). • Duration: 6-48 hr. • Protein Bound: 95%.• Bioavailability: 29%.

MAO-B inhibitors • Selegiline • Conventional 5 mg PO at breakfast & 5 mg at lunch (10 mg/day). Not to

exceed 10 mg/day. • Orally-disintegrating (with levodopa/carbidopa). Initial 1.25 mg PO qDay, may increase after 6 weeks if inadequate

response, no more than 2.5 mg/day. The main pharmacokinetics parameters • Peak plasma time: (conventional) 0.5-0.9 hr; (ODT) 15-40 min. • Half-life elimination: 10 hr (PO); 18-25hr (TD). • Duration: 24-72hr (PO). • Bioavailability: 10%. • Protein Bound: 90%.• Vd: 300 L. • Metabolism: cytochrome P-450 enzymes. • Excretion: Urine.

MAO-B inhibitors• Rasagiline at a dosage of 1 mg once daily is given

as monotherapy. The main pharmacokinetics parameters• Half-Life elimination: 1.3-3 hr.• Peak Plasma Time: 1 hr. • Bioavailability: 36%. • Protein Bound: 88-94%.• Vd: 87 L. • Metabolism: liver, primarily CYP1A2 (in vitro data). • Excretion: Urine (62%); feces (7%).

COMT Inhibitors• Tolcapone The usual dosage is 100-200 mg PO q8hr. Always as an

adjunct to levodopa/carbidopaThe main pharmacokinetics parameters• Peak Plasma Time: 2 hr. • Bioavailability: 65-85%.• Protein Bound: >99.9%. • Half-life elimination: 2-3hr. • Vd: 9 L. • Metabolism: Liver glucuronidation. • Excretion: Urine (60%); feces (40%).

COMT Inhibitors• Entacapone • The usual dosage is 200 mg PO with each dose of

levodopa/carbidopa• Not to exceed 1600 mg/day.The main pharmacokinetics parameters• Peak Plasma Time: 1 hr. • Bioavailability: 35%.• Protein Bound: 98%. • Vd: 20 L. • Half-life elimination: 0.4-0.7 hr (B-phase); 2.4 hr

(Y-phase). • Metabolism: Hepatic glucuronidation. • Excretion: Feces (90); urine (10%).

Nonopioid Analgesics Para-aminophenol derivative

Acetaminophen650–1000 mg q 6–8 h

Pharmacokinetics• Peak Plasma Time:

10-60 min 8 hr (PO 650 mg, extended-release tablet)

• Peak Plasma Concentration: 1.8 -2.1 mcg/mL • Distribution: 1 L/kg• Protein Bound: 10 to 25%

• Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic/sulfuric acid)

• Half-life elimination: 1.25-3 hr• Excretion: urine

• Time to Peak:Oral: 10-60 minutesIV: 15 minutes

NSAIDThe main pharmacokinetics parameters

of indoles

Diclofenac• Bioavailability: 50-60%• Protein Bound:

99-99.8%

• Vd: 1.3-1.4 L/kg• Metabolism: liver

(hydroxylation and conjugation with glucuronic acid, taurine amide, sulfuric acid)

• Half-life: 1.2-2 hr• Excretion:

urine 50-70% feces 30-35%

Indomethacin• Bioavailability: 100%• Onset: 30 min• Duration: 4-6 hr• Protein Bound: 99%• Vd: 0.34-1.57 L/kg• Metabolism: Liver• Half-life:

1 hr (initial phase); 2.6-11.2 hr (2 phase)

• Excretion: urine 60%

feces >33%


Nabumetone• Onset: Several days

• Protein Bound: >99%

• Vd: 29-82L • Metabolism: Hepatic

• Half-life elimination: 24 hr

• Excretion: urine (80%)

feces (9%)

Piroxicam• Half-life:14-158 hr (average

50 hr)

• Onset: 15-30 min -1 hr

• Duration: 48-72 hr• Protein Bound: 99.3%• Vd: 0.12-0.14 L/kg• Metabolism: hydroxylation;

conjugation by cyclodehydration

• Excretion: urine, feces


• e

Ibuprofen Ketoprofen Naproxen

Half-life 2-4 hr 2-4 hr

Onset 30-60 min <30 1 hr

Duration 4-6 hr 6 hr 4-7 hr

Vd 0.12 L/kg 0.1 L/kg 0.16 L/kg

Protein Bound 90-99% 99% <99%

Bioavailability

80-100% 90% 95%

Metabolism Rapid hepatic oxidation

hepatic hepatic conjugation

Excretion Urine 50-60% (<10% unchanged)

Urine 50-90% feces 1-8%

Urine 95%; feces <5%


• e

Aspirin Meclofenamate

Half-life 2-3 hr (low dose); 15-30 hr (higher dose)

40 min-5.3 hr

Onset PO 5-30 min; PR 1-2 hr 30 min

Duration PO 3-6 hr PR >7 hr

Vd 0.15-0.2 L/kg

Protein Bound

90-95% 99.8%

Bioavailability

80-100% 26%

Metabolism Hepatic via microsomal enzyme system

Hepatic

Excretion principally in urine (80-

100%), saliva, feces urine (70%); feces (20-30%)

Opioid Analgesics The main pharmacokinetics parameters

Phenylbutazone

Ketorolac Celecoxib

Half-life 60 hr 2-6 hr 11 hr

Onset IM: 10 min; PO: 30-60 min

Duration 6-8 hr

Vd 0.11-0.33 L/kg 7.14 L/kg

Protein Bound

98% >99% 97%

Bioavailability

80-100% undetermined

Metabolism hepatic hepatic hepatic (CYP2C9)

Excretion urine Urine (91%); feces

feces 57%; urine 27%


Codeine Hydrocodone Propoxyphene Half-life: 3-5 hrOnset: RapidDuration: 2-4 hr (SC/IM)Peak Plasma Time: SC 40-60 min; IM 30-50 minBioavailability: 50-60%; Protein Bound: 60-80%Metabolism: liver Excretion: urine (primarily)

Half-life: 3.3-4.4 hrDuration: 4-8 hrPeak Plasma Time: 1.3 hr (single 10 mg dose)Concentration: 23.6 ng/ml (single 10 mg dose)Metabolism: liver

Excretion: urine

(mainly)

Half-life: 6-12 hrDuration: 4-6 hrPeak Plasma Time: 2-2.5 hrConcentration: 50-120 ng/mLMetabolism: prolonged, hepaticExcretion: urine (primarily)


Fentanyl Levorphanol

Half-life 2-4 hr 12-16 hr

Onset immediate (IV)7-15 min (IM)

10-60 min (PO)

Duration 1-2hr (IM); 0.5-1hr (IV)

4-8 hr

Vd

Protein Bound 80-85%

Bioavailability

50%

Metabolism hepatic hepatic

Excretion urine (75%), feces urine


Meperidine

Methadone

Morphine

Half-life 0.5-1 hr 8-59 hr 1.5-4.5 hr

Onset 30-60 min (PO); 10-30 min (IM)

0.5-1 hr (oral); 10-20 min (parenteral)

15-30 min (PO); <5 min (IV)

Duration 4-6 hr 4-6 hr up to 7 hr

Vd 3.5 L/kg (PO); 2.6 L/kg (IM)

1-4.7 L/kg (IV)

Protein Bound

25% 85-90% 36% (IV)

Bioavailability

36-100%

Metabolism liver liver liver

Excretion urine, feces urine urine & feces

pharmacokinetics ampicillinceftriaxonevancomycin half-life: 1-1.8 hr protein bound: 15-25%...

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