Hydroxychloroquine and Lyme

Int Microbiol 2002 Mar;5(1):25-31

An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine.

Brorson O, Brorson SH.

Department of Microbiology, Vestfold Sentralsykehus, Tonsberg, Norway.

In this work the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine (HCQ) was studied.

These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of HCQ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi.

PMID: 12102233 [PubMed - in process]

Hydroxychloroquine - Chloroquine

Pharmacokinetic Data

Source: Goodman & Gilman's "The Pharmacological Basis of Therapeutics", 9th edition (1996)


AVAILABILITY (ORAL) (%): 89 ± 16
BOUND IN PLASMA (%): 61 ± 9;  ´ rheumatoid arthritis
CLEARANCE (CL/F, ml * min-1 * kg-1): 1.8 ± 0.4b
VOL. DIST. (Vss/F, liters/kg): 115 ± 61b
HALF-LIFE (t1/2, hours): 41 ± 14 daysb,c
EFFECTIVE CONCENTRATIONS: 15 ng/mld;  30 ng/mle


a Active metabolite, desethylchloroquine, accounts for 20 ± 3% of urinary excretion; t1/2 = 15 ± 6 days.
b Blood CL/F, Vss/F, and t1/2; blood-to-plasma concentration ratio = 9.
c Shorter half-lives reported previously when sampling stopped after 1 month.
d Plasmodium vivax.
e Plasmodium falciparum.
f Diplopia; dizziness.

White, N.J. Clinical pharmacokinetics of antimalarial drugs. Clin. Pharmacokinet., 1985, 10:187-215.

(added by J. Gruber)

Half Life

Chloroquine is safer when given orally because the rates of absorption and distribution are more closely matched; The half-life of chloroquine increases as plasma levels decline, reflecting the transition from slow distribution to even slower elimination from extensive tissue stores.

Volume of Distribution V

V = amount of drug in body / C


  1. plasma volume of a typical 70-kg man is 3 liters,
  2. blood volume is about 5.5 liters,
  3. extracellular fluid volume outside the plasma is 12 liters, and
  4. the volume of total body water is approximately 42 liters.
However, many drugs exhibit volumes of distribution far in excess of these values(, indicative of the fact that these drugs have preferentially entered compartments other than 1. - 4.).

If 500 mg of digoxin were in the body of a 70-kg subject, a plasma concentration C of approximately 0.7 ng/ml would be observed. Dividing the amount of drug in the body (500 mg) by the plasma concentration (0.7 ng/ml) yields a volume of distribution for digoxin of about 700 liters, or a value ten times greater than the total body volume of a 70-kg man.
In fact, digoxin, which is relatively hydrophobic, distributes preferentially to muscle and adipose tissue and to its specific receptors, leaving a very small amount of drug in the plasma.

Enrichment in Tissue, Brain, Spinal Cord

(from Product Information for chloroquine phosphate (ARALENE) distributed by Sanofi Winthrop Pharmaceuticals, Park Ave, New York, NY 10016, USA)

In animals the concentration 200 ... 700 times the plasma concentration may be found in

Chloroquine is also enriched in leukocytes.

The concentration in

is only 10 ...30 times the concentration in plasma.

Explanations of usage of terms Clearance, Volume of Distribution, Half-Life

(added by J. Gruber)

Following GG, General Principles, Chapter "Clinical Pharmacokinetics" in Leslie Benet "Pharmacokinetics" .

CL = Clearance from blood compartment (ml per minute)
(the notion used is that every minute a volume CL (ml) is removed (and freed of drug) from the volume of distribution Vss)
In GG-Appendix II, the "plasma clearance" for cephalexin is reported as CL/F = 4.3 ml  min-1 kg-1,
with 91% of the drug excreted unchanged in the urine.
For a 70-kg man, the "total body clearance from plasma" CL = 300 ml/min,
with renal clearance accounting for 91% of this elimination.
In other words, the kidney is able to excrete cephalexin at a rate such that approximately 273 ml of plasma would be freed of drug per minute.

Because clearance usually is assumed to remain constant in a stable patient, the total rate of elimination of cephalexin will depend on the concentration of drug in the plasma (equation 1-2).

useful definitions:

  • Clearance

  • CL = (rate of elimination by specified route) / (Concentration in specified compartment)
  • Elimination half life

  • t1/2 = ln2/k = ln2 Vss/CL

    CL = k Vss and
    k = CL/Vss (= fraction of Vss removed per minute)

  • Diff. eq. describing elimination:

  • dm/dt = - k m

    (in GG k m is called "rate of elimination")
    (equation 1-2)
    rate of elimination = C CL =

                                         = C k Vss =
                                         = k C Vss = k m

with the following nomenclature:
C  = concentration of drug in blood (g drug/ml blood)
CL =  clearance ((ml blood / l volume of distribution) / minute)
k = elimination constant,
m = mass of drug (g)
rate of elimination = dm/dt = change of mass of drug in Vss per unit time


(1) Dosage for malaria
(from Product Information for ARALEN Phosphate (chloroquine phosphate), distributed by Sanofi Winthrop Pharmaceuticals, Park Ave, New York, NY 10016, USA)

Dosage may be taken in as multiples of D = 5 mg base per kg body weight, but D should not exceed 300 mg base:

  1. first dose: 2 D,
  2. 6 hours after the first dose: D.
  3. 18 hours after the second dose: D,
  4. 24 hours after the third dose: D .
So, the total dose is: 5 D = 25 mg base per kg body weight.

(2) Estimate of dosage to achieve a 32 microg/ml  concentration of free Chloroquine in blood (enrichment 1, i.e. no enrichment), tissue (enrichment 200), brain (enrichment 10)

During approx. 2 half-lives the intake has to fill up the volume of distribution Vss = 100 l/kg 70 kg = 7 103 l.


the total amount of the drug taken in has to be intake1

intake1 = 32 microg/ml Vss = 224 g of base


the intake has to be 2 intake1:

necessary intake = 2 intake1 = 448 g.

The dosage estimate is 448 g/ (2 t1/2).

Although the high volume of distribution tells us that chloroquine distributes into compartments other than 1. - 4, and the concentration in those compartments is probably higher than the concentrations in blood, the GG data do not tell us how low the concentration in blood can be to yield a concentration of 32 microg/ml in Bb cyst infected tissue.

Using the enrichment data from Sanofi  and assuming an elimination half life t1/2 = 41 + 14 days = 55 days, we will arrive at the following approximate dosages (numbers in parentheses ( ) apply to a half life t1/2 = 41 - 14 days = 27 days)

  1. dosage = 4000 (8000) mg/day for 32 microgram/ml in blood,
  2. dosage = 20 (40) mg/day for 32 microgram/ml in tissue,
  3. dosage = 400 (800) mg/day for 32 microgram/ml in brain.
The dosage to obtain 32 microgram/ml in blood is higher than the dose (approximately 1000 mg/day) recommended for adults having malaria (see also Medline literature search, keywords "hydroxychloroquine/adverse effects"[All Fields] AND dosage).

When less than 4000 (8000) mg per day are taken in, the blood compartment might not be bactericidal for mobile spirochetes, if the Brorsons' in vitro data are applicable to the in vivo situation. One has to keep in mind: This is a very rough dose estimate that aimes at providing us a hint as to whether or not HCQ can be discussed as a drug against Lyme disease.

Further Reading

Version: August 19, 2008 Joachim Gruber
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